Prognostic interaction between ASXL1 and TET2 mutations in chronic myelomonocytic leukemia.

Blood Cancer Journal
Mrinal M PatnaikA Tefferi

Abstract

Mutations involving epigenetic regulators (TET2~60% and ASXL1~40%) and splicing components (SRSF2~50%) are frequent in chronic myelomonocytic leukemia (CMML). On a 27-gene targeted capture panel performed on 175 CMML patients (66% males, median age 70 years), common mutations included: TET2 46%, ASXL1 47%, SRSF2 45% and SETBP1 19%. A total of 172 (98%) patients had at least one mutation, 21 (12%) had 2, 24 (14%) had 3 and 30 (17%) had >3 mutations. In a univariate analysis, the presence of ASXL1 mutations (P=0.02) and the absence of TET2 mutations (P=0.03), adversely impacted survival; while the number of concurrent mutations had no impact (P=0.3). In a multivariable analysis that included hemoglobin, platelet count, absolute monocyte count and circulating immature myeloid cells (Mayo model), the presence of ASXL1 mutations (P=0.01) and absence of TET2 mutations (P=0.003) retained prognostic significance. Patients were stratified into four categories: ASXL1wt/TET2wt (n=56), ASXL1mut/TET2wt (n=31), ASXL1mut/TET2mut (n=50) and ASXL1wt/TET2mut (n=38). Survival data demonstrated a significant difference in favor of ASXL1wt/TET2mut (38 months; P=0.016), compared with those with ASXL1wt/TET2wt (19 months), ASXL1mut/TET2wt (21 months)...Continue Reading

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Citations

Feb 6, 2016·Blood Cancer Journal·M M Patnaik, A Tefferi
Apr 12, 2016·Leukemia & Lymphoma·Mrinal M Patnaik, Ayalew Tefferi
Jul 15, 2017·American Journal of Hematology·Rangit VallapureddyMrinal M Patnaik
Aug 2, 2018·Current Hematologic Malignancy Reports·Aziz Nazha, Mrinal M Patnaik
May 12, 2018·Leukemia·Mrinal M PatnaikGuillermo Garcia-Manero
Mar 31, 2019·Cellular and Molecular Life Sciences : CMLS·Shuhei AsadaToshio Kitamura
Sep 10, 2019·British Journal of Hospital Medicine·Yanhong QiaoBei Liu
May 17, 2019·Current Hematologic Malignancy Reports·Hany Elmariah, Amy E DeZern
Nov 19, 2019·American Journal of Hematology·Mrinal M Patnaik, Ayalew Tefferi
Jan 23, 2020·International Journal of Molecular Sciences·Christina K FerroneMichael J Rauh
Sep 9, 2017·Oncotarget·Nicoletta CoccaroFrancesco Albano
Jun 6, 2020·British Journal of Haematology·Daniel Moreno BerggrenElisabeth Ejerblad
Nov 17, 2016·Current Opinion in Oncology·Ana AlfonsoGuillermo Garcia-Manero
Aug 20, 2017·Current Hematologic Malignancy Reports·Aaron C Shaver, Adam C Seegmiller
May 9, 2019·Disease Models & Mechanisms·Evisa GjiniA Thomas Look
Nov 16, 2019·Current Oncology Reports·Giacomo Coltro, Mrinal M Patnaik
May 18, 2016·American Journal of Hematology·Mrinal M Patnaik, Ayalew Tefferi
Jul 22, 2018·Annals of Laboratory Medicine·Hyun Young KimHee Jin Kim
Oct 13, 2018·Current Hematologic Malignancy Reports·Sanam Loghavi, Joseph D Khoury
Feb 7, 2019·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Daniel A Arber, Attilio Orazi
Aug 9, 2018·Leukemia·Mrinal M PatnaikGuillermo Garcia-Manero
Sep 29, 2019·Advances in Cell and Gene Therapy·Abhishek A Mangaonkar, Mrinal M Patnaik
Jun 8, 2018·American Journal of Hematology·Mrinal M Patnaik, Ayalew Tefferi
Dec 5, 2020·Hematology·Mrinal M Patnaik, Terra L Lasho
Aug 5, 2019·Leukemia Research·Sang Mee HwangDong Soon Lee
May 29, 2020·Best Practice & Research. Clinical Haematology·Onyee Chan, Eric Padron
Dec 5, 2020·Expert Review of Hematology·Thomas P ThomopoulosVasiliki Pappa

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Methods Mentioned

BETA
biopsies
biopsy
MDS

Software Mentioned

Genome Analysis Toolkit ( GATK
Stat View
Genesifter
RTA

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