A primitive hematopoietic cell is the target for the leukemic transformation in human philadelphia-positive acute lymphoblastic leukemia

C Cobaleda, N Gutierrez-Cianca… - Blood, The Journal …, 2000 - ashpublications.org
C Cobaleda, N Gutierrez-Cianca, J Pérez-Losada, T Flores, R Garcıa-Sanz, M Gonzalez
Blood, The Journal of the American Society of Hematology, 2000ashpublications.org
BCR-ABL is a chimeric oncogene generated by translocation of sequences from the
chromosomal counterpart (c-ABL gene) on chromosome 9 into the BCR gene on
chromosome 22. Alternative chimeric proteins, BCR-ABLp190 and BCR-ABLp210, are
produced that are characteristic of chronic myelogenous leukemia (CML) and Philadelphia
chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). In CML, the transformation
occurs at the level of pluripotent stem cells. However, Ph1-ALL is thought to affect progenitor …
BCR-ABL is a chimeric oncogene generated by translocation of sequences from the chromosomal counterpart (c-ABLgene) on chromosome 9 into the BCR gene on chromosome 22. Alternative chimeric proteins, BCR-ABLp190 and BCR-ABLp210, are produced that are characteristic of chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph1-ALL). In CML, the transformation occurs at the level of pluripotent stem cells. However, Ph1-ALL is thought to affect progenitor cells with lymphoid differentiation. Here we demonstrate that the cell capable of initiating human Ph1-ALL in non-obese diabetic mice with severe combined immunodeficiency disease (NOD/SCID), termed SCID leukemia–initiating cell (SL-IC), possesses the differentiative and proliferative capacities and the potential for self-renewal expected of a leukemic stem cell. The SL-ICs from all Ph1-ALL analyzed, regardless of the heterogeneity in maturation characteristics of the leukemic blasts, were exclusively CD34+CD38, which is similar to the cell-surface phenotype of normal SCID-repopulating cells. This indicates that normal primitive cells, rather than committed progenitor cells, are the target for leukemic transformation in Ph1-ALL.
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