Page 19 - Haematologica March 2020

Editorials
tions and their prognostic contribution in chronic myelomonocytic leukemia: a two-center study of 466 patients. Leukemia. 2014;28(11):2206-2212.
4. Elena C, Gallì A, Such E, et al. Integrating clinical features and genet- ic lesions in the risk assessment of patients with chronic myelomonocytic leukemia. Blood. 2016;128(10):1408-1417.
5. Patnaik MM, Vallapureddy R, Lasho TL, et al. EZH2 mutations in chronic myelomonocytic leukemia cluster with ASXL1 mutations and their co-occurrence is prognostically detrimental. Blood Cancer J. 2018;8(1):12.
6. Patnaik MM, Barraco D, Lasho TL, et al. DNMT3A mutations are associated with inferior overall and leukemia-free survival in chronic myelomonocytic leukemia. Am J Hematol. 2017;92(1):56-61.
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Leukemia stem cell gene expression signatures contribute to acute myeloid leukemia risk stratification
Katherine L. B. Knorr and Aaron D. Goldberg
Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA E-mail: AARON D. GOLDBERG - goldbera@mskcc.org
doi:10.3324/haematol.2019.241117
The majority of patients with acute myeloid leukemia (AML) will die of their disease. Nevertheless, the prognosis of AML varies widely. Some AML patients may be cured by chemotherapy alone, while others require approaches such as allogeneic stem cell transplantation to have the best chance of long- term survival. As physicians, we are often asked by our AML patients: “How likely is this treatment going to work, and how long do I have to live?”1
Prognostication in AML has evolved over time. Initially, models for prediction of response to therapy were based on patient’s parameters such as age and performance sta- tus in combination with cell characteristics such as mor- phology and chromosomal karyotype. With technologi- cal advancements, our understanding of disease biology has evolved and factors including molecular mutations and minimal residual disease have been integrated into prognostication schemes. Recently, an international expert panel on behalf of the European LeukemiaNet (ELN) published a revised version of a widely utilized prognostication scheme that categorizes AML patients into three risk groups (Favorable, Intermediate, and Adverse) based on genetic abnormalities (incorporating chromosomal karyotype and specific molecular muta-
tions).2 These AML risk groups have profound clinical implications, particularly with regard to post-remission therapy for younger fit patients. In general, fit Favorable- risk AML patients who achieve a first complete remission after induction chemotherapy go on to consolidation chemotherapy with curative intent. However, even fit patients with Adverse- and Intermediate-risk AML are unlikely to be cured by chemotherapy alone, and there- fore it is reasonable to consider allogeneic stem cell trans- plantation for Intermediate- and Adverse-risk patients upon achievement of first complete remission.
Why is AML so often resistant to chemotherapy? The biology of AML chemoresistance is complex. However, at a basic level, adverse-risk AML cells are more likely to evade conventional chemotherapeutics that target the cell cycle. It has therefore been hypothesized that one pow- erful driver of adverse prognosis in AML may be the properties of the leukemia stem cell (LSC), a type of cell that exhibits cell cycle quiescence, self-renewal, and chemoresistance.3-6 Although AML LSC remain challeng- ing to isolate, assessment of AML LSC gene expression signatures has been proposed as a method to further refine prognosis – with LSC-like AML phenotypes con- tributing to adverse risk.
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