ASXL1 mutations are frequent and prognostically detrimental in CSF3R‐mutated chronic neutrophilic leukemia. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Elliott, Michelle A.; Pardanani, Animesh; Hanson, Curtis A.; Lasho, Terra L.; Finke, Christy M.; Belachew, Alem A.; Tefferi, Ayalew
• Is Part Of: American journal of hematology. Volume 90:Issue 7(2015:Jul.)
• Page Start: 653
• Page End: 656
• Publication Date: 2015-07
• Subjects: Hematology -- Periodicals; 616.15
• DOI: 10.1002/ajh.24031
• Languages: English
• ISSNs: 0361-8609

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Colony stimulating factor 3 receptor gene (<italic>CSF3R</italic>) mutations have recently been associated with chronic neutrophilic leukemia (CNL). Fourteen patients with <italic>CSF3R</italic>‐mutated CNL (median age 67 years; 57% males) were screened for additional mutations; 8 (57%) and 5 (38%) harbored an <italic>ASXL1</italic> and/or <italic>SETBP1</italic> mutation (two patients expressed both), respectively. Two patients developed blastic transformation, both <italic>SETBP1‐</italic>mutated and <italic>ASXL1‐</italic>unmutated, whereas two other cases evolved into chronic myelomonocytic leukemia (CMML), both <italic>ASXL1</italic>‐mutated and <italic>SETBP1‐</italic>unmutated. Median survival was 23.2 months (10 deaths documented). On multivariable analysis mutated <italic>ASXL1</italic> (<italic>P</italic> = 0.009; HR 19.6, 95% CI 2.1–184.1) and thrombocytopenia (<italic>P</italic> = 0.005; HR 28.8, 95% CI 2.8–298.2) were independently predictive of shortened survival. This study provides information on the natural history of <italic>CSF3R</italic>‐mutated CNL and identifies mutant <italic>ASXL1</italic> and thrombocytopenia as risk factors for survival. The study also suggests pathogenetic roles for <italic>SETBP1</italic> and <italic>ASXL1</italic> mutations in disease evolution into blast phase disease and CMML, respectively. Am. J. Hematol. 90:653–656, 2015. © 2015 Wiley Periodicals, Inc.</p> </abstract>