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Blood, Vol. 95 No. 3 (February 1), 2000:
pp. 1007-1013
A primitive hematopoietic cell is the target for the leukemic
transformation in human Philadelphia-positive acute lymphoblastic
leukemia
C. Cobaleda,
N. Gutiérrez-Cianca,
J. Pérez-Losada,
T. Flores,
R. García-Sanz,
M. González, and
I. Sánchez-García
From the Departamento de Proliferación y Diferenciación
Celular, Instituto de Microbiología Bioquímica;
Servicio de Anatomía Patológica; and Servicio de
Hematología, Universidad de Salamanca, Salamanca, Spain.
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 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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