Insights into the New Molecular Updates in Acute Myeloid Leukemia Pathogenesis

Abstract

As our understanding of the biologic basis of acute myeloid leukemia evolves, so do the classification systems used to describe this group of cancers. Early classification systems focused on the morphologic features of blasts and other cell populations; however, the explosion in genomic technologies has led to rapid growth in our understanding of these diseases and thus the refinement of classification systems. Recently, two new systems, the International Consensus Classification system and the 5th edition of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues, were published to incorporate the latest genomic advances in blood cancer. This article reviews the major updates in acute myeloid leukemia in both systems and highlights the biologic insights that have driven these changes.

Keywords: acute myeloid leukemia; genomics; molecular updates; pathogenesis.

Figure 1

Schematic diagram depicting the CEBPA gene structure and distribution of mutations. ATG p42 and p30 denote the locations of the initiation codon for the p42 and p30 isoforms of CEBPA, respectively. TAD1—transactivation domain 1; TAD2—transactivation domain 2; DBD—DNA binding domain; bZIP—basic leucine zipper domain. p. positions refer to the protein position in the p42 isoform encoded by NCBI transcript NM_004364.

Figure 2

Pathogenic mechanism of progression in germline SAMD9/SAMD9L mutation. (A) Hematopoietic stem cell harboring germline gain-of-function SAMD9/SAMD9L mutation on chromosome 7. (B) In response to cellular stress, there is selective pressure for reversion via loss of chromosome 7 (monosomy), reversion mutation of SAMD9/SAMD9L, or uniparental disomy in the region of the mutation. (C) Cells that lose chromosome 7 are at risk of acquiring additional hits and progressing to a myeloid neoplasm. Created with BioRender.com.