The role of microenvironment in the initiation and evolution of B-cell precursor acute lymphoblastic leukemia

Abstract

B cell precursor acute lymphoblastic leukemia (BCP-ALL) is a malignant disorder of immature B lineage immune progenitors and is the commonest cancer in children. Despite treatment advances it remains a leading cause of death in childhood and response rates in adults remain poor. A preleukemic state predisposing children to BCP-ALL frequently arises in utero, with an incidence far higher than that of transformed leukemia, offering the potential for early intervention to prevent disease. Understanding the natural history of this disease requires an appreciation of how cell-extrinsic pressures, including microenvironment, immune surveillance and chemotherapy direct cell-intrinsic genetic and epigenetic evolution. In this review, we outline how microenvironmental factors interact with BCP-ALL at different stages of tumorigenesis and highlight emerging therapeutic avenues.

Obesity, bone marrow adiposity, and leukemia: Time to act

“…Adulthood obesity is a critical modifiable risk factor for AML and MDS, (a group of clonal hematological dysfunctions causing dysplastic and inefficient hematopoiesis). 226,227 BMSCs isolated from patients with MDS and AML exhibit a decreased delta-like non-canonical notch ligand 1 or delta-like homolog-1 (DLK1, a transmembrane protein) level that is an early negative regulator of adipogenic cell fate inhibitor in MDS and AML BMSCs. 228 The BMSCs differentiate into adipocytes in DLK1 deficient MDS and AML patients.…”