Immature acute leukaemias: lessons from the haematopoietic roadmap

Abstract

It is essential to relate the biology of acute leukaemia to normal blood cell development. In this review, we discuss how modern models of haematopoiesis might inform approaches to diagnosis and management of immature leukaemias, with a specific focus on T-lymphoid and myeloid cases. In particular, we consider whether next-generation analytical tools could provide new perspectives that could improve our understanding of immature blood cancer biology.

Role of developmental pathways in disease

“…Continuing on the theme of blood cancers, the review by Thomas Lefeivre et al . [15] covers the relationship between blood cell development and acute leukemia. The authors discuss the limitations of current diagnostic methods with emerging knowledge on normal blood development and molecular alterations that drive tumorigenesis and reflect on how to incorporate modern sequencing tools to define more precisely and treat specific types of acute leukemia.…”

Polycomb Alterations in Acute Myeloid Leukaemia: From Structure to Function

“…While genetic alterations in PRC1 factors are rare, reduced function of PRC2 due to mutation or deletion is common in acute myeloid leukaemia (AML) and the immature subgroup of T-acute lymphoblastic leukaemia (T-ALL), as well as the rarer T/myeloid mixed phenotype acute leukaemia (MPAL) subtype. While PRC2 alterations are known to be linked to poor outcomes and resistance to existing chemotherapies in both AML and T-ALL [ 22 , 23 , 24 , 25 , 26 ], the precise molecular mechanisms of these effects are not fully understood. In this review, we explore the recent findings on the molecular effects of epigenetic disruption linked to PRC2 alterations in AML, with reference to structural features of the PRC2 complex, and highlight the lacunae in this field.…”