Multistep pathogenesis of chronic myelomonocytic leukemia in patients.

Content Provider	Europe PMC
Author	Geissler, Klaus Jäger, Eva Barna, Agnes Gurbisz, Michael Marschon, Renate Graf, Temeida Nösslinger, Thomas Pfeilstöcker, Michael Machherndl‐Spandl, Sigrid Stauder, Reinhard Zebisch, Armin Sill, Heinz Öhler, Leopold Kusec, Rajko Hoermann, Gregor Valent, Peter
Abstract	AbstractBackgroundA multistep pathogenesis of myeloid leukemia including mutations in epigenetic, spliceosome, and signaling genes has been recently demonstrated in a preclinical model but is poorly validated in patients.MethodsClinical, phenotypic, and biologic features were compared between three distinct molecularly defined CMML cohorts including TET2 monomutated patients (T, n = 10), TET2/SRSF2 bimutated patients (TS, n = 19), and patients who had NRAS mutations in addition to TET2/SRSF2 comutations (TSN, n = 14).ResultsMedian survival was 90, 45, and 9 months, respectively (p = .001). Whereas no patient in the T and TS group transformed into acute myeloid leukemia (AML), 6/14 patients in the TSN group had AML at study entry or transformed during follow‐up. Leukocyte counts, blast cell counts, and LDH levels were significantly higher in TSN vs. TS and T, respectively, whereas hemoglobin and platelet values were not significantly different. Increased growth factor‐independent myeloid colony formation was restricted to TSN but not found in T and TS, respectively. The proportion of patients showing in vitro myelomonocytic skewing in T, TS, and TSN was 0%, 56%, and 100%, respectively (p = .010).ConclusionOur results demonstrate that the model of multistep pathogenesis in CMML can be recapitulated in patients regarding clinical, phenotypic, and biologic features.
Related Links	https://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC9310570&blobtype=pdf
Page Count	8
ISSN	09024441
Journal	European Journal of Haematology [Eur J Haematol]
Volume Number	109
DOI	10.1111/ejh.13768
PubMed Central reference number	PMC9310570
Issue Number	1
PubMed reference number	35299281
e-ISSN	16000609
Language	English
Publisher	John Wiley and Sons Inc.
Publisher Date	2022-03-23
Publisher Place	Hoboken
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. © 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.
Subject Keyword	CMML NRAS pathogenesis SRSF2 TET2
Content Type	Text
Resource Type	Article
Subject	Hematology