Leukemogenesis in Acute Lymphoblastic Leukemia through the Lens of Developmental Dynamics of Lymphoid Progenitor Cells: a systematic review

ObjectiveThe objective of this study is to investigate how lymphoid progenitor mechanisms contribute to the leukemogenesis in Acute Lymphoblastic Leukemia. BackgroundAcute Lymphoblastic Leukemia (ALL), the leading childhood cancer, remains challenging despite treatment advances. ALL originates from aberrant clonal expansion of immature lymphoid progenitor cells (LPCs) due to genetic abnormalities. This study looks into LPC genetic dysregulations, aiming to identify therapeutic targets and enhance prognostic stratification. Understanding ALL pathogenesis not only improves outcomes but also informs broader cancer research, offering potential insights for hematologic malignancies and oncogenesis, promising advancements in clinical practice. MethodsDatabases, including PubMed, MEDLINE, Google Scholar, and open access/subscription-based journals were searched for published articles without any date restrictions, to investigate leukemogenesis in acute lymphoblastic leukemia and the impact of down syndrome through the developmental regulators of lymphoid progenitor cells. Based on the criteria mentioned in the methods section, studies were systematically reviewed to investigate ALL leukemogenesis. This study adheres to relevant PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). ResultsAcute Lymphoblastic Leukemia (ALL) development is marked by dysregulations in key factors governing Lymphoid Progenitor Cells (LPCs) proliferation and differentiation. Dysregulations include upregulation of transcription factors Ikaros and PU.1, along with heightened expression of surface markers CD34 and CD38. Increased levels of signaling molecules IL-7, SCF, and FLT3 Ligand drive LPC proliferation, while alterations in epigenetic modifiers DNMTs, HDACs, and HATs further contribute to uncontrolled cell division. Dysregulated transcription factors Ikaros, PU.1, E2A (TCF3), EBF1, and Notch1 disrupt LPC differentiation pathways, alongside aberrant expression of surface markers CD10, CD7, and CD45RA. Dysregulated signaling through IL-7 and the Notch pathway, along with epigenetic modifications mediated by DNMTs, HDACs, and HATs, collectively create a conducive landscape for ALL development. ConclusionThis study into the origins of ALL investigates the roles of transcription factors, surface markers, signaling molecules, and epigenetic modifiers in LPC proliferation and differentiation. Dysregulation of these components, often due to mutations in genes like GATA1, CRLF2, JAK2, and RAS, disrupts normal hematopoietic development and leads to leukemic transformation.