Next-generation sequencing technology reveals a characteristic pattern of molecular mutations in 72.8% of chronic myelomonocytic leukemia by detecting frequent alterations in TET2, CBL, RAS, and RUNX1.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
Alexander KohlmannTorsten Haferlach

Abstract

Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that is characterized by features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Thus far, data on a comprehensive cytogenetic or molecular genetic characterization are limited. Here, we analyzed 81 thoroughly characterized patients with CMML (CMML type 1, n = 45; CMML type 2, n = 36) by applying next-generation sequencing (NGS) technology to investigate CBL, JAK2, MPL, NRAS, and KRAS at known mutational hotspot regions. In addition, complete coding regions were analyzed for RUNX1 (beta isoform) and TET2 aberrations. Cytogenetic aberrations were found in 18.2% of patients (14 of 77 patients). In contrast, at least one molecular mutation was observed in 72.8% of patients (59 of 81 patients). A mean of 1.6 mutations per patient was observed by this unprecedented screening. In total, 105 variances were detected by this comprehensive molecular screening. After excluding known polymorphisms or silent mutations, 82 distinct mutations remained (CBL, n = 15; JAK2V617F, n = 8; MPL, n = 0; NRAS, n = 10; KRAS, n = 12; RUNX1, n = 7; and TET2, n = 41). With respect to clinical data, a better outcome was seen for patients carrying TET2 mutation...Continue Reading

References

Jul 19, 2002·Blood·Ulrich GermingNorbert Gattermann
Sep 14, 2004·Leukemia & Lymphoma·U GermingN Gattermann
Aug 2, 2005·Nature·Marcel MarguliesJonathan M Rothberg
Jan 7, 2006·Leukemia & Lymphoma·Miloslav BeranElihu Estey
Jul 4, 2007·Haematologica·Ulrich GermingJohn M Bennett
Feb 28, 2009·Clinical Chemistry·Karl V VoelkerdingJacob D Durtschi
May 29, 2009·The New England Journal of Medicine·François DelhommeauOlivier A Bernard
Jun 2, 2009·Nature Genetics·Saskia M C LangemeijerJoop H Jansen
Aug 12, 2009·Blood·Olivier KosmiderUNKNOWN Groupe Francophone des Myélodysplasies
Oct 3, 2009·Haematologica·Olivier KosmiderUNKNOWN Groupe Francophone des Myélodysplasies

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Citations

Mar 3, 2010·Annals of Hematology·Ulrike BacherTorsten Haferlach
Sep 10, 2011·Annals of Hematology·Luz Martínez-AvilésBeatriz Bellosillo
Sep 27, 2012·Annals of Hematology·Juliana SchwaabAndreas Reiter
Oct 2, 2012·Molecular Diagnosis & Therapy·Raoul TibesRuben A Mesa
Sep 29, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Leonardo BoiocchiAttilio Orazi
Jan 12, 2013·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Elizabeth L CourvilleRobert P Hasserjian
Feb 26, 2011·Bioinformatics·Hans-Ulrich KleinMartin Dugas
Jun 7, 2012·Transfusion Medicine and Hemotherapy : Offizielles Organ Der Deutschen Gesellschaft Fur̈ Transfusionsmedizin Und Immunham̈atologie·Christian GabrielJohannes Pröll
May 4, 2011·The Journal of Clinical Investigation·Romain AucagneLaurent Delva
Aug 28, 2013·The Journal of Clinical Investigation·Susumu GoyamaJames C Mulloy
Dec 14, 2011·Hematology·Mario CazzolaRosangela Invernizzi
Dec 14, 2011·Hematology·Timothy Graubert, Matthew J Walter
Dec 7, 2011·PloS One·Xiongwei CaiNancy A Speck
Nov 23, 2013·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Renata LukackovaBeata Mladosievicova
Mar 14, 2014·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M T W TeoA E Kiltie
Feb 11, 2014·Best Practice & Research. Clinical Haematology·Raphael ItzyksonEric Solary
Nov 29, 2013·Epigenomics·Alexander LairdRichard R Meehan
May 9, 2014·The Journal of Clinical Investigation·Guangyao KongJing Zhang
Sep 1, 2012·Annual Review of Pathology·R Coleman Lindsley, Benjamin L Ebert
Mar 15, 2012·Cellular and Molecular Life Sciences : CMLS·Jean-Noël BastieLaurent Delva
Feb 18, 2016·Leukemia & Lymphoma·Mette Vestergaard ElbækHans Carl Hasselbalch

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