Involvement of primary mesenchymal precursors and hematopoietic bone marrow cells from chronic myeloid leukemia patients by BCR-ABL1 fusion gene.

For decades now, it is well established that chronic myeloid leukemia (CML) is a hematopoietic stem cell (HPC) disorder. However, it remains to be determined whether BCR-ABL1 gene rearrangement occurs in a HPC or at an earlier stem cell and whether the degree of involvement of hematopoiesis by the BCR-ABL1 fusion gene relates to the response to therapy. Here, we have investigated by interphase fluorescence in situ hybridization (iFISH) the distribution of BCR-ABL1 fusion gene in FACS-sorted bone marrow (BM) populations of mesenchymal precursor cells (MPC) and other hematopoietic cell populations from 18 newly diagnosed CML patients. Overall, our results showed systematic involvement at relatively high percentages of BM maturing neutrophils (97%+/- 15%), basophils (95%+/- 12%), eosinophils (90%+/- 8%), CD34(+) precursors cells (90%+/- 7%), monocytes (84%+/- 30%), nucleated red blood cells (87%+/- 24%), and mast cells (77%+/- 33%). By contrast, MPC (30%+/- 34%), B-cells (15%+/- 27%), T-lymphocytes (50%+/- 26%), and NK-cells (35%+/- 34%) were involved at lower percentages. In 8/18 CML patients, 2 tumor BCR-ABL1(+) subclones were detected by iFISH. Of note, all tumor cell subclones were systematically detected in CD34(+) cells, whereas MPC were only involved by the ancestral tumor cell subclone. In summary, here we confirm the presence at diagnosis of the BCR-ABL1 fusion gene in MPC, CD34(+) precursors, and other different BM hematopoietic myeloid cell lineages from CML patients, including also in a significant fraction of cases, a smaller percentage of T, B, and NK lymphocytes. Interestingly, involvement of MPC was restricted to the ancestral BCR-ABL1(+) subclone. Am. J. Hematol. 89:288-294, 2014. (c) 2013 Wiley Periodicals, Inc.