BCR-ABL EXPRESSION IS REDUCED IN THE PRIMITIVE PRECURSOR FRACTION FROM CML TKI-TREATED PATIENTS.

MARÍA SOL RUIZ; BAFFA TRASCI SOFIA; BEATRIZ MOIRAGHI; MARIEL PEREZ; RUBEN BURGOS; CECILIA FONCUBERTA; CAROLINA PAVLOVSKY; JOSE MORDOH; IRENE LARRIPA; JULIO SANCHEZ AVALOS; MARIANA GONZALEZ, PATRICIA GARGALLO, MICHELE BIANCHINI, CARLOS DE BRASI Y IRENE LARRIPA.

Viena

Congreso; 20th Congress of the European Hematology Association.; 2015

Background: Insensitivity to imatinib is a property exhibited by a population of leukemic rare, primitive stem cells that are present in most chronic myeloid leukemia (CML) patients, even in those with sustained undetectable molecular residual disease (UMRD). It remains unclear whether such patients are definitively cured or whether leukemic stem cells (LSCs)that persist in their bone marrow represent a risk of disease recurrence. This suggests that the characterization of LSCsby functional assays could be of interest in clinical practice.Aims: To evaluate the burden of LSCs in TKI-treated patients.Methods: We evaluated the presence of LSCs in patients with CML at different levels of molecular response induced by imatinib or nilotinib, and patients naïve of treatment. All patients gave their informed consent. Bone marrow-derived CD34+ cells were used as initiators for 2-week CFU-C and 6-week long-term culture-initiating cell (LTC-IC) assays. Their phenotype was defined using RT-qPCR on individual (8-10 colonies per patient) and pooled colonies (24-30 colonies per patient).Results: In samples from newly diagnosed patients, BCR-ABL mRNA expression was measured in individual colonies from CFU-C assays (mean %BCR-ABL/ABL=24.0, SD=7.3, n=4). However, in LTC-IC assays, BCR-ABL mRNA only became detectable when measured in pools of 3-15 colonies (mean %BCR-ABL/ABL =6.6%, SD=9.6, n=3). BCR-ABL mRNA levels were highly variable in LTC-IC-derived pooled CFU-Cs, but still lower than in 2-week CFU-Cs (ANOVA,p