The Role of hnRNPs in Acute Myeloid Leukemia Thesis

The circulatory system serves to integrate all the organs responsible for hematopoiesis and the execution of various duties related to blood. The components of this system encompass blood, red bone marrow, the thymus, the spleen, lymph nodes, lymphoid tissue found in non-hematopoietic organs, as well as blood cells present in connective and epithelial tissues (Maloy & Hughes, 2013). The various components of the system exhibit close interdependence and adhere to the overarching principles of neurohumoral control, displaying both genetic and functional interconnectedness. The comprehension of the blood system encompasses an examination of its operations and roles, as well as an exploration of the development and structure of its constituent constituents.

The lymphatic and immunological systems have a tight interrelationship with the circulatory system. Immunocytes are generated inside the hematopoietic organs and afterwards undergo circulation and recirculation within the peripheral blood and lymphatic system. Blood and lymph are types of connective tissues that originate from mesenchyme. They are composed of plasma and corpuscles that are suspended within it, and together they create the interior environment of the body (Maloy & Hughes, 2013). The continual interchange of chemicals, including those present in the plasma, occurs between the blood and lymph due to their intimate interconnection. Lymphocytes undergo recirculation between the bloodstream and the lymphatic system, while all blood cells originate from pluripotent stem cells.

Hematopoiesis

The differentiation of blood cells from pluripotent stem cells takes place both during embryogenesis and postnatally. The aforementioned stages are referred to as embryonic hematopoiesis and postembryonic hematopoiesis. Embryonic hematopoiesis is a physiological process that takes place throughout the embryonic stage, characterized by the development of blood as a distinct tissue. During this phase, several organs inside the body participate in the process of hematopoiesis, which involves the production of blood cells. Postembryonic hematopoiesis is a blood regeneration process that takes place after birth (Maloy & Hughes, 2013). Postembryonic hematopoiesis encompasses the maturation processes of many blood cell types, including erythrocytes, granulocytes, platelets, monocytes, lymphocytes, and immunocytes. These processes are referred to as erythropoiesis, granulocytopoiesis, thrombocytopoiesis, monocytopoiesis, lymphocytopoiesis, and immunocytopoiesis, respectively.

Hematopoiesis is a lifelong process that persists in individuals. The primary role of this entity is to facilitate the production and regeneration of hematopoietic cells, which are essential for fulfilling the body's daily requirements and safeguarding against potential harm, such as trauma or infection (Maloy & Hughes, 2013). Hematopoiesis is a highly dynamic and intricate biological process, wherein the adult human body generates a staggering quantity of blood cells on a daily basis. Specifically, this process yields approximately one trillion blood cells, comprising 200 billion red blood cells and 70 billion neutrophils, as reported by Maloy and Hughes (2013). The regulation of hematopoiesis involves the examination of distinct processes, such as stochastic and instructive mechanisms, which are investigated individually.

Hematopoietic stem and progenitor cells (HSPCs) are a type of cells that have the ability to differentiate into several blood cell types.

Significant emphasis should be placed on the haematopoietic stem and progenitor cells, as they hold a pivotal position in the hematopoietic process. Hematopoietic stem cells (HSCs) might be metaphorically positioned at the apex of the hematopoietic hierarchy. The two key traits possessed by these entities are self-renewal and the capacity for multipotent differentiation into all mature bloodlines (Maloy & Hughes, 2013). Self-renewal is a biological process characterized by cellular division, resulting in the generation of two hematopoietic stem cells (HSCs). On the other hand, differentiation refers to the developmental process wherein cells give rise to many specialized blood cell types, including erythrocytes, platelets, lymphocytes, monocytes, and granulocytes.

Since the 1950s, researchers have been actively engaged in the investigation of hematopoiesis through the study of hematopoietic stem cells (HSCs). The restoration of hematopoiesis in irradiated animals has been demonstrated by research conducted on mice, indicating the involvement of cells from both the spleen and bone marrow (Maloy & Hughes, 2013). Subsequently, the notion of chimerism was proposed, which refers to the reconstitution of host cells by the incorporation of donor cells (Maloy & Hughes, 2013). Moreover, during the 1960s, a groundbreaking revelation was made regarding the phenomenon of self-renewal shown by individual clonogenic cells within the bone marrow. This self-renewal process subsequently led to the restoration of hematopoiesis. The existence of hematopoietic stem cells (HSCs) in vivo was proposed by Till et al. (1964) and further supported by Till and McCulloch (1980). Moreover, this discovery played a crucial role in the later clinical transplantation of hematopoiesis.

The regulation of hematopoiesis by transcription factors

It is important to reiterate that hematopoietic stem cells (HSCs) are primarily situated within the bone marrow and play a crucial role in the regulation of the entire respiratory system, occupying the highest position in the hierarchy of blood cells. During the process of embryonic hematopoiesis, the definitive hematopoietic stem cells (HSCs) are generated from the mesodermal tissue and then colonize the fetal liver prior to their migration towards the brain. The conclusion was reached by scientists based on the data acquired from studies of hematopoiesis in mice (Wilkinson & Göttgens, 2013). During the postembryonic phase of hematopoiesis, hematopoietic stem cells (HSCs) remain quiescent and maintain their inherent capacities for self-renewal, division, proliferation, and differentiation into several adult hematopoietic cell types (Wilkinson & Göttgens, 2013). The transcriptional regulation plays a crucial role in governing the specification and cellular selection of hematopoietic stem cells (HSCs) during their developmental process. Transcriptional regulators are observed to be present during several stages of hematopoietic stem cell (HSC) processes, including specification, expansion, homeostasis, and differentiation. The aforementioned entities encompass transcription factors, effectors of signaling pathways, and moderators of epigenetics.

Researchers are currently examining transcription factors in the context of embryonic hematopoiesis, with a focus on elucidating the mechanisms involved in hematopoietic stem cell (HSC) production throughout fetal development and hematopoietic stages. A transcriptional network governs the emergence of blood cells, incorporating the requisite transcription factors essential for hematopoiesis. The transcriptional network encompasses a multitude of variables that play a crucial role in the regulation of hematopoiesis. The key constituents of these variables include ETV2, SCL, and RUNX1 (Wilkinson & Göttgens, 2013). Hence, their indispensability in the process of blood cell production precludes their exclusion. Each factor exerts regulatory control over a specific and well-defined stage in the specification of the hematopoietic process, such as the germ layer of the mesoderm or the development of fully functioning blood precursors.

In order to design protocols for the creation of blood cells de novo, scientists needed to possess knowledge regarding the process of hematopoiesis, with a specific focus on transcriptional regulation. According to Menegatti et al. (2019), the investigation of the process has also encompassed the reprogramming of somatic cells or the direct programming of pluripotent stem cells (p. 3304). Significantly, the laboratory-based cell creation process exhibits notable distinctions from its analogous physiological counterpart.

The regulation of hematopoiesis by growth factor

Hematopoietic cells possess multipotency as they have the capacity to differentiate into many cell lineages. The ultimate constituents of these cellular lineages give rise to the cells of the blood and immune system. Hematopoietic cells, as described by Lee et al. (2020), play a crucial role in the regulation of the proliferation and differentiation processes of both red and white blood cells. The cellular growth regulatory factors included by these cells consist of the stem cell factor (SCF), a cytokine implicated in the proliferation and self-renewal of hematopoietic cells, as well as erythropoietin and colony-stimulating factors (CSFs), which elicit the generation of blood cells (Lee et al., 2020). Hematopoietic stem cells (HSCs) have the remarkable ability to generate new blood cells in a continuous manner, a process that persists throughout the lifespan of an organism owing to their inherent capacities for self-renewal and differentiation. The regulation of hematopoiesis is governed by the intricate microenvironment present within the bone marrow niche. The microenvironment in question comprises many cellular components found within the bone marrow, which are subject to regulation by growth factors and cytokines. The process of hematopoiesis occurring inside the microenvironment is referred to as bone marrow niche homeostasis.

The dysregulation observed in the haematopoietic system.

Hematopoietic stem cells (HSCs) play a crucial role in continuously supplying the blood system with mature hematopoietic cells over the course of an individual's lifespan. Additionally, they serve as a reservoir for replenishing the hematopoietic system in cases of acute blood loss, providing the body with a means to immediately restore blood supply. Complex regulatory processes have emerged in order to ensure the continuous generation of hematopoietic cells during evolution. According to Basilico and Göttgens (2017), these programs are responsible for regulating the processes of differentiation and self-renewal in hematopoietic stem and progenitor cells (HSPCs). Dysregulation may manifest when leukemogenic mutations impair regulatory programs. According to Basilico and Göttgens (2017), these mutations have the potential to impede the process of cellular differentiation while concurrently promoting cellular proliferation. The regulatory mechanisms of hematopoietic stem and progenitor cells (HSPCs) can be perturbed by leukemogenic fusion genes harboring a mixed lineage leukemia gene (MLL). In the context of hematopoiesis, the bone marrow serves as the site where regulatory programs and hematopoietic stem and progenitor cells (HSPCs) reside in a quiescent state, playing a crucial role in maintaining the equilibrium of hematopoiesis.

Acute Myeloid Leukemia 

Acute myeloid leukemia (AML) is a highly aggressive malignancy characterized by the uncontrolled proliferation of myeloid cells. Leukemia is a malignancy affecting the white blood cells, and the designation "acute leukemia" is employed to characterize the swift and aggressive advancement of this neoplastic condition. Hence, expeditious intervention is vital for the management of leukemia, given the substantial mortality risks associated with the swift progression of the ailment (Acute myeloid leukemia, 2021). Acute leukemia can be classified based on the specific leukocyte population that is impacted. There exist two primary categories of white blood cells, namely lymphocytes and myeloid cells. Lymphocytes are responsible for combating viral infections, while myeloid cells exhibit a broader range of tasks encompassing the defense against bacterial infections, the prevention of tissue damage, and the protection of the body against parasitic organisms.

Initially, it is necessary to elucidate the manifestations of Acute Myeloid Leukemia (AML), which ensue from a proliferation of immature leukocytes, progress gradually over a span of multiple weeks, and then intensify rapidly. The symptoms associated with acute myeloid leukemia encompass various manifestations, including pallor of the skin, dyspnea, weariness, profuse perspiration, unintended weight loss, elevated body temperature, recurrent febrile episodes, heightened susceptibility to infections, frequent episodes of bleeding (e.g., gingival or nasal hemorrhage), as well as the presence of flat erythematous or purpuric lesions on the skin (Acute myeloid leukemia, 2021). In addition to the aforementioned symptoms, individuals may also present with a tendency to bruise easily, as well as bone and joint pain. Abdominal discomfort may also be experienced, along with the presence of enlarged glands in the neck, armpits, or groin. Furthermore, patients may report pain upon palpation of the affected glands.

The etiology of acute myeloid leukemia (AML) 

Etiology is the academic discipline concerned with the study of the origins of diseases, encompassing the examination of the conditions and factors that contribute to their occurrence. The genesis of acute myeloid leukemia is multifaceted and will be delineated in the subsequent discussion. Acute myeloid leukemia (AML) arises as a result of a genetic alteration occurring in hematopoietic stem cells (HSC) located in the bone marrow. The mutation leads to an excessive production of immature white blood cells by HSCs, rendering them incapable to effectively combating infections (Acute myeloid leukemia, 2021). The symptoms mentioned above arise as a consequence of diminished levels of healthy red blood cells and platelets in the bloodstream, which can be attributed to an augmented influx of immature cells. Simultaneously, the etiology of genetic mutation in Acute Myeloid Leukemia (AML) remains elusive. Multiple risk factors associated with the onset of acute myeloid leukemia (AML) have been found by scientific researchers.

The following are risk factors associated with high levels of radiation exposure, specifically in the context of getting radiation therapy as a component of cancer treatment. Benzene, a compound commonly present in gasoline and frequently emitted inside the rubber industry, represents an additional significant cause of danger. Furthermore, it is noteworthy that benzene is included in cigarette smoke, hence contributing to the heightened susceptibility of smokers to Acute Myeloid Leukemia (AML) (Acute myeloid leukemia, 2021). The administration of chemotherapy medications for the treatment of other types of malignancies is also considered a risk factor. Additional risk factors include hematological abnormalities such as myelodysplasia, myelofibrosis, or polycythemia vera, as well as genetic disorders such as Down syndrome and Fanconi's anemia.

The diagnostic process for Acute Myeloid Leukemia (AML)

The diagnosis of acute myeloid leukemia (AML) necessitates the implementation of various diagnostic procedures due to the intricate nature of the disease. During the initial phases of diagnosis, the therapist conducts a comprehensive assessment to identify physical indicators, which encompass the aforementioned symptoms, and necessitates the administration of a blood test. The test results suggest the potential presence of leukemia when aberrant white blood cells or a significantly reduced blood count are observed. In such a scenario, the therapist makes a referral to a hematologist who does supplementary tests in order to obtain further clarification regarding the diagnosis (Acute myeloid leukemia, 2021). A bone marrow biopsy is a subsequent procedure conducted to validate the diagnosis of acute myeloid leukemia (AML) following a series of preliminary testing. In this examination, the physician employs a slender needle to extract a specimen of fluid bone marrow, which is subsequently extracted from the posterior region of the femur. Subsequently, the bone marrow specimen is examined for the presence of malignant cells. In the event that these cells are detected, the physician utilizes the identical sample to ascertain the specific classification of leukemia.

As the disease advances, medical professionals employ several diagnostic procedures, including genetic testing, imaging scans, and lumbar puncture, to gather additional data pertaining to the progression and severity of acute myeloid leukemia (AML). Genetic testing plays a crucial role in the identification of the specific subtype of acute myeloid leukemia (AML), whereby blood and bone marrow specimens are subjected to diagnostic examination ("Acute myeloid leukemia," 2021). In order to evaluate the condition of the lungs and heart and make informed decisions regarding subsequent medical interventions, it is imperative to conduct a cardiac examination employing either X-ray or ultrasound imaging techniques. This diagnostic procedure serves to analyze the general well-being of these vital organs. A lumbar puncture procedure is employed to assess the potential for the dissemination of acute myeloid leukemia (AML) to the central nervous system. During this procedure, a medical professional utilizes a needle to extract cerebrospinal fluid, which is subsequently examined for the presence of malignant cells. The presence of cancer cells has implications for the subsequent course of treatment.

The classification and clinical features of acute myeloid leukemia (AML).

The categorization of acute myeloid leukemia (AML) exhibits distinctions from the conventional staging classification employed for other types of malignancy. In conventional medical practice, the stage of cancer is commonly seen as a critical factor in assessing the extent of its dissemination. The stage at which an individual is situated can have an impact on their whole well-being, encompassing both emotional and mental states. This knowledge is crucial in determining appropriate subsequent treatment options (Hwang, 2020). Acute myeloid leukemia typically does not give rise to neoplastic growths, and is commonly observed to be diffusely distributed within the bone marrow, and occasionally, in the liver and spleen (Hwang, 2020). Hence, the classification of AML is based on laboratory tests, rather than being categorized according to phases. The prognosis of acute myeloid leukemia (AML) is influenced by various factors, including the age and overall health status of the patient, as well as the results of additional diagnostic tests. Furthermore, the specific subtype of AML also plays a role in determining the prognosis.

The pharmaceutical interventions employed for the various subtypes of acute myeloid leukemia (AML) typically exhibit variations. There are two primary systems employed for the classification of Acute Myeloid Leukemia (AML): the French-American-British (FAB) classification and the classification established by the World Health Organization (WHO). The FAB classification system was created during the 1970s to categorize leukemia into several subtypes ranging from M0 to M7. This classification scheme differentiates between the specific cell types from which the leukemia originates and also takes into account signs of cellular maturity (Hwang, 2020). The formation of this system was achieved by the utilization of microscopic examination of cells. Based on this categorization, M0 represents undifferentiated acute myeloid leukemia, M1 corresponds to acute myeloblastic leukemia with minimal maturation, M2 denotes acute myeloblastic leukemia with maturation, M3 signifies acute promyelocytic leukemia, M4 represents acute myelocytic leukemia, and M4 eos designates acute myelomonocytic leukemia with eosinophilia. In the classification system, M5 represents acute monocytic leukemia, M6 denotes acute erythroid leukemia, and M7 signifies acute megakaryoblastic leukemia.

The World Health Organization (WHO) classification, in contrast to the French-American-British (FAB) classification, incorporates prognostic criteria and was established in the year 2016. Hence, the process of classification involves the identification of certain criteria that contribute to a more streamlined comprehension of various disease types (Hwang, 2020). As to the categorization provided by the World Health Organization (WHO), Acute Myeloid Leukemia (AML) can be categorized into two subtypes based on specific chromosomal abnormalities. The first subtype is characterized by a translocation event occurring between chromosomes 8 and 21, while the second subtype is characterized by a translocation or inversion event involving chromosome 16 (Hwang, 2020). The aforementioned conditions include Acute Promyelocytic Leukemia (APL) characterized by a hybrid PML-RARA gene, Acute Myeloid Leukemia (AML) with a translocation involving chromosomes 9 and 11, AML with a translocation between chromosomes 6 and 9, AML with a translocation or inversion of chromosome 3, AML (megakaryoblastic) with a translocation between chromosomes 1 and 22, and AML with a mutated NPM1 gene.

Additionally, there exist cases of acute myeloid leukemia (AML) characterized by a mutant RUNX1 gene, AML displaying alterations linked to myelodysplasia, and AML that arises as a consequence of prior exposure to chemotherapy or radiation therapy. The various types of acute myeloid leukemia (AML) include AML unless otherwise specified, AML with minimal differentiation (FAB M0), AML without maturation (FAB M1), AML with maturation (FAB M2), acute myelomonocytic leukemia (FAB M4), acute monoblastic/monocytic leukemia (FAB M5), pure erythroid leukemia (FAB M6), and acute megakaryoblastic leukemia (FAB M7) (Hwang, 2020). The classification scheme also include acute basophilic leukemia, acute panmyellosis with fibrosis, myeloid sarcoma, and myeloid proliferation that is associated with Down's syndrome. Excluded from the categorization of undifferentiated kinds are leukemias known as mixed phenotype leukemias, characterized by the presence of both lymphocytic and myeloid characteristics.

The management of acute myeloid leukemia (AML)

Treatment is initiated promptly upon confirmation of diagnosis, owing to the quickly progressive nature of the disease. Acute myeloid leukemia (AML) is a multifaceted ailment that necessitates the involvement of a diverse group of experts for its treatment (Acute myeloid leukemia, 2021). The therapy regimen comprises of two distinct phases, namely induction and consolidation. During the process of induction, physicians strive to eradicate a substantial number of leukemia cells present in the bloodstream and bone marrow with the objective of halting the manifestation of symptoms and preventing untimely mortality. During the consolidation phase, physicians are tasked with the objective of preventing the reoccurrence of leukemia and eradicating any leftover leukemia cells. In certain instances, it may be necessary to repeat the induction phase multiple times before to commencing the consolidation process.

In cases when the likelihood of problems is elevated, healthcare providers may opt to administer less intensive chemotherapy regimens or explore alternate treatment modalities. The induction phase relies on the lack of problems and the feasibility of administering intensive chemotherapy, wherein the patient is administered a large dosage of a combination of two or more medications (Acute myeloid leukemia, 2021). Typically, patients are subjected to two cycles of induction, which involve the administration of intense chemotherapy, within a hospital or another healthcare setting. During the duration of the courses, healthcare professionals engage in the practice of medical supervision, administering regular blood transfusions to patients in order to maintain an adequate level of healthy blood cells. Currently, the patient is susceptible to infections and is being maintained in a hygienic and controlled medical setting.

Conventional therapeutic approaches in the treatment of acute myeloid leukemia (AML)

Conventional therapy is founded upon techniques that were created during the 1970s and encompasses a rigorous initiation protocol involving the administration of cytarabine and anthracycline. Following the induction stage, patients go to the consolidation stage, wherein chemotherapy treatment involving large doses of cytarabine is administered (Acute myeloid leukemia, 2021). Patients with poor signs, namely those with high or intermediate risks, are recommended for allogeneic hematopoietic stem cell transplantation (HSCT) due to the increased likelihood of relapse when treated solely with chemotherapy. This particular methodology demonstrates a curative efficacy of 35-45% among individuals below the age of 60, while exhibiting a significantly lower success rate of fewer than 15% among patients aged 60 and above. Simultaneously, it is observed that the mean age at the point of diagnosis for acute myeloid leukemia (AML) is 68 years (Acute myeloid leukemia, 2021). Hence, a substantial cohort of patients is precluded from receiving rigorous therapy or allogenic hematopoietic stem cell transplantation (HSCT) due to the significantly heightened mortality risk.

Hence, therapy modalities that have demonstrated efficacy for this particular cohort encompass low-dose cytarabine (LDAC) and DNA methyltransferase inhibitors (Acute myeloid leukemia, 2021). It is worth mentioning that the average survival within the cohort ranges from 6 to 10 months after undergoing such therapy. Hence, it is advised by researchers to investigate the potential of targeted therapy as an alternative approach, as certain treatment protocols devoid of chemotherapy have demonstrated a near-perfect remission rate of almost 100% and a long-term survival rate of 98% (Acute myeloid leukemia, 2021). As previously stated, the standard therapy protocol encompasses the sequential phases of induction and consolidation.

The utilization of targeted therapy in the treatment of acute myeloid leukemia (AML)

The nomenclature "targeted therapy" is derived from its distinctive characteristic of being specialized and applicable alone to particular types of mutations. The prevailing forms of targeted therapy encompass FLT3 inhibitors, IDH1 and IDH2 inhibitors, RAS inhibitors, KIT inhibitors, agents that target the apoptotic pathway such as BCL2 and MCL1 inhibitors, MDM2 inhibitors, immunological therapy, and monoclonal antibodies that specifically target leukemia surface antigens. It is worth mentioning that mutations in the FLT3 gene are prevalent among approximately 33% of newly diagnosed patients with Acute Myeloid Leukemia (AML) (Acute myeloid leukemia, 2021). Mutations in the IDH1 and IDH2 genes have been observed in around 5-15% and 10-15% of individuals who have recently been diagnosed with acute myeloid leukemia (AML). Furthermore, it is noteworthy that mutations in KRAS or NRAS are detected in approximately 10-25% of patients upon initial diagnosis, while KIT mutations are observed in up to 25% of patients (Acute myeloid leukemia, 2021).

Heterogeneous Nuclear Ribonucleoprotein (hnRNP)

Heterogeneous nuclear ribonucleoproteins (hnRNPs) encompass a collection of RNA-binding proteins. The multifunctionality of these proteins can be attributed to the intricate and varied nature of heterogeneous nuclear ribonucleoproteins (hnRNPs). Short et al. (2020) have reported that the individuals in question are engaged in the intricate process of converting heterogeneous nuclear RNAs (hnRNAs) into fully developed messenger RNAs (mRNAs). Heterogeneous nuclear ribonucleoproteins (hnRNPs) also have a role in the modulation of gene expression as transcription factors. The aforementioned RNA-binding proteins, which are primarily nuclear in nature, commonly establish associations with transcripts of RNA polymerase II. They engage in a multitude of biological processes, such as the transcription and processing of pre-mRNA within the nucleus. Additionally, they participate in the process of translating and transporting mRNA within the cytoplasm.

This paper provides an overview of heterogeneous nuclear ribonucleoproteins (hnRNPs), which are a group of RNA-binding proteins that play crucial roles in several cellular

The hnRNPs possess various essential roles, which encompass the prevention of pre-mRNA folding into secondary structures, the transportation of mRNA from the nucleus, the regulation of the cell surface glycoprotein CD44, and the interaction with telomeres. Short et al. (2020) have reported that multiple human genes are responsible for encoding heterogeneous nuclear ribonucleoproteins (hnRNPs), and the functional variety of these hnRNPs is determined by the various families they belong to. Research is now being conducted on each hnRNP family, with a focus on elucidating the mechanisms behind the functioning of each hnRNP and investigating the factors contributing to their involvement in DNA damage.

The Structure and Function of hnRNPs

Heterogeneous nuclear ribonucleoproteins (hnRNPs) play a significant role in regulating the cell cycle and responding to DNA damage. Functions encompass the processes of recruitment, splicing, and co-regulation pertaining to the diverse repertoire of proteins that govern the progression of the cell cycle. The significance of hnRNPs in regulating the cell cycle renders them capable of functioning as an oncogene (Short et al., 2020). The loss of hnRNPs function has been implicated in the development of various types of cancer. Errors in splicing often arise as a result of the impairment of hnRNPs' functional capacity. Nevertheless, certain heterogeneous nuclear ribonucleoproteins (hnRNPs) play a crucial role in the recruitment and coordination of proteins.

The Significance of Heterogeneous Nuclear Ribonucleoproteins in Physiological Hematopoiesis

Recent studies have elucidated the essential features of hnRNPs, shedding light on their involvement in several regulatory pathways (Short et al., 2020). Heterogeneous nuclear ribonucleoproteins (hnRNPs) are macromolecular complexes consisting of RNA and protein components. These complexes are localized within the cell nucleus and play a crucial role in the process of gene transcription. Following the process of gene transcription, a subsequent phase of post-transcriptional modification takes place, involving the alteration of the recently produced RNA, commonly referred to as pre-mRNA (Short et al., 2020). The presence of these proteins linked to the pre-mRNA molecule signifies the immaturity of the pre-mRNA, suggesting that it has not undergone complete processing and is therefore not prepared for export to the cytoplasm. The proteins that are involved in the formation of hnRNPs complexes are referred to as heterogeneous ribonucleoproteins.

The Significance of Heterogeneous Nuclear Ribonucleoproteins in the Pathogenesis of Acute Myeloid Leukemia

Researchers are currently directing their attention towards the investigation of hnRNPs and their potential involvement in the process of DNA damage. The aforementioned methodology has the potential to be a significant advancement in elucidating the precise etiology of acute myeloid leukemia (AML) across many subtypes, hence facilitating the progress of more sophisticated and evidence-based treatment modalities (Short et al., 2020). The investigation of heterogeneous nuclear ribonucleoproteins (hnRNPs) has significant promise due to their demonstrated involvement in the degradation of DNA and the disruption of crucial hematopoietic stem cell (HSC) processes, resulting in heightened generation of immature leukocytes, a defining feature of acute myeloid leukemia (AML).

The purpose and goals

The objective of this thesis is to investigate the involvement of heterogeneous nuclear ribonucleoproteins (hnRNPs) in the pathogenesis of acute myeloid leukemia. Ongoing research in this field is being actively pursued, emphasizing its significant significance due to the very limited proportion of patients achieving complete remission. The senior population represents the primary demographic in which Acute Myeloid Leukemia (AML) is initially diagnosed, and unfortunately, has a notably low rate of remission. Hence, the objective of this thesis is to present a comprehensive analysis of the scholarly publications investigating the involvement of hnRNPs in acute myeloid leukemia. The primary aim is to succinctly describe the key ideas conveyed in these articles and arrange the gathered information in a structured manner, such as through the utilization of tables or diagrams, to facilitate future research endeavors.

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