Evidence of ABL-kinase domain mutations in highly purified primitive stem cell populations of patients with chronic myelogenous leukemia

Biochemical and Biophysical Research Communications
N SorelA G Turhan

Abstract

To study the hierarchical levels of stem cell targets for ABL-kinase domain mutations in CML, highly purified CD34+CD38- and CD34+CD38+ cell populations and their LTC-IC-derived progeny were analyzed in four patients at diagnosis (n=1) or in advanced phases (n=3) of their disease. In the single patient with early phase CML who later developed an Imatinib Mesylate-resistance and a Y253H mutation, no mutation was detectable in purified cell fractions analyzed at diagnosis nor in their LTC-IC-derived progeny. In contrast, in three patients in advanced phase CML, ABL-kinase mutations demonstrated in peripheral blood cells by sequencing (Q252E and M351T) were detectable in the FACS-sorted cells and became amplified in the LTC-IC-derived progeny of the primitive cells. These findings demonstrate that in late CP or advanced CML, ABL-kinase mutations occur as an intraclonal event in the primitive Ph1+ stem cell compartments with progression of this clone towards IM-resistant blast phase.

Citations

Sep 24, 2010·Leukemia·I SlomaC J Eaves
May 2, 2007·Journal of the National Cancer Institute·Xiaoyan JiangConnie Eaves
Dec 16, 2010·The Journal of Clinical Investigation·Amie S CorbinBrian J Druker
Dec 17, 2008·Hematology·Catriona H Jamieson
Apr 10, 2008·Leukemia & Lymphoma·François GuilhotAli Turhan
Nov 26, 2015·International Journal of Molecular Sciences·Elzbieta Pawlowska, Janusz Blasiak
Mar 30, 2010·Journal of Photochemistry and Photobiology. B, Biology·Sirinart Chio-SrichanMatthieu Refregiers
Mar 27, 2007·Clinical Lymphoma & Myeloma·François GuilhotFrederic Millot
Mar 27, 2007·Clinical Lymphoma & Myeloma·Xiaoyan JiangConnie Eaves
Jan 11, 2012·American Journal of Hematology·Mary AlikianLetizia Foroni
Apr 13, 2010·Biochemical Pharmacology·Rajesh R NairLori A Hazlehurst
Mar 10, 2015·Protein & Cell·Hong Zhou, Rongzhen Xu
May 29, 2016·Chinese Journal of Cancer·Zhi-Jie KangQuentin Liu
Mar 5, 2010·Journal of Experimental & Clinical Cancer Research : CR·Ai-Hua WangJun-Min Li

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