HemaBites showcase hematology news and short commentaries on recent high-impact articles published in international journals. This blog will keep you up to date with the latest developments and discoveries in the field of hematology.

Monday, December 3, 2018

Discovering clonal diversity in acute myeloid leukemia

​Discovering clonal diversity in acute myeloid leukemia

Jan Cools, VIB-KU Leuven Center for Cancer Biology, Editor-in-chief HemaSphere

Acute myeloid leukemia (AML) development is driven by the accumulation of mutations and chromosomal rearrangements in hematopoietic stem or progenitor cells. As a consequence, multiple clones emerge and evolve during AML progression and one of these clones may reappear at relapse. Bauke de Boer, Jan Jacob Schuringa and colleagues have now developed new tools to enable the tracking, isolation and characterization of such AML subclones1. They used a proteomic analysis to identify suitable cell surface markers that are specifically expressed or upregulated on AML blasts and leukemia stem cells. Based on these markers, different subclones could be isolated by cell sorting and sequence analysis revealed that the different sublcones within one AML patient harbored different mutations. In one AML case, for example, CD34+CD25+ cells were isolated that harbored DNMT3A, RUNX1, IDH2 and FLT3 mutation, while CD34+CD25- cells harbored the same mutations, except the FLT3 mutation. They next also performed gene expression and chromatin analyses in those different subclones and observed that dependent on the presence or absence of specific mutations different transcriptional programmes were active in the cells. The authors were also able to correlate response to therapy or growth characteristics with the presence or absence of certain mutations. Finally, the cell surface markers were also used to track subclones during treatment and eventually at relapse, illustrating their applicability in longitudinal studies. This approach with cell sorting based on selected cell surface markers is maybe less fancy than single-cell sequencing2, but is by no means less interesting!

1. de Boer B, Prick J, Pruis MG, Keane P, Imperato MR, Jaques J, et al. Prospective Isolation and Characterization of Genetically and Functionally Distinct AML Subclones. Cancer Cell, 2018;34(4):674-689.
2. Wilson NK, Göttgens B. Single-Cell Sequencing in Normal and Malignant Hematopoiesis. HemaSphere, 2018;2(2):e34.