Recent Progress in Chronic Neutrophilic Leukemia and Atypical Chronic Myeloid Leukemia
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Purpose of Review
We reviewed recent diagnostic and therapeutic progress in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We summarized recent genetic data that may guide future efforts towards implementing risk-adapted therapy based on mutational profile and improving disease control and survival of affected patients.
Recent genetic data in CNL and aCML prompted modifications to the World Health Organization (WHO) diagnostic criteria, which have improved our understanding of how CNL and aCML are different diseases despite sharing common findings of peripheral granulocytosis and marrow myeloid hyperplasia. The overlap of recurrently mutated genes between aCML and CMML support considering CSF3R-T618I mutated cases as a distinct entity, either as CNL or CNL with dysplasia. Ongoing preclinical and clinical studies will help to further inform the therapeutic approach to these diseases.
Our understanding of CNL and aCML has greatly advanced over the last few years. This will improve clarity for the diagnosis of these diseases, provide a strategy for risk stratification, and guide risk-adapted therapy.
KeywordsChronic neutrophilic leukemia Atypical chronic myelogenous leukemia Colony-stimulating factor 3 receptor (CSF3R) JAK-STAT signaling Myelodysplasia/myeloproliferative neoplasm (MDS/MPN)
K.T.D. is supported by the Knight Cancer Institute. J.W.T. is supported by the Leukemia & Lymphoma Society, the V Foundation for Cancer Research, Gabrielle’s Angel Foundation for Cancer Research, and the National Cancer Institute (5R00CA151457-04; 1R01CA183947-01). J.G. is supported by the Charles and Ann Johnson Foundation.
Compliance with Ethical Standards
Conflict of Interest
All authors on this manuscript are investigators of the NCT02092324 clinical trial evaluating the safety and efficacy of ruxolitinib (Incyte Corporation) in patients with aCML and CNL. Incyte is providing financial support of this trial. The authors do not perceive any conflict of interest in their presentation of data and preparation of this manuscript. K.T.D. and J.G. additionally serve on advisory board activities sponsored by Incyte and receive honoraria in support of their participation.
Jeffrey W. Tyner reports grants from Agios, Aptose, Array, AstraZeneca, Constellation, Genentech, Incyte, Janssen, Seattle Genetics, Syros, Takeda, and other from Leap Oncology outside the submitted work.
Kim-Hien T. Dao and Jason R. Gotlib reports grants and other from Incyte Corporation outside the submitted work.
Human and Animal Rights and Informed Consent
This article contains no studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
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