Evidence of ABL-kinase domain mutations in highly purified primitive stem cell populations of patients with chronic myelogenous leukemia
N Sorel, ML Bonnet, M Guillier, F Guilhot… - Biochemical and …, 2004 - Elsevier
N Sorel, ML Bonnet, M Guillier, F Guilhot, A Brizard, AG Turhan
Biochemical and biophysical research communications, 2004•ElsevierTo 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 …
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 …
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.
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