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Acute leukemia after a primary myelodysplastic syndrome: immunophenotypic,
genotypic, and clinical characteristics [see comments]
JF San Miguel, JM Hernandez, R Gonzalez-Sarmiento, M Gonzalez, I Sanchez, A Orfao, MC Canizo and A Lopez Borrasca
Hospital Clinico de Salamanca, Departamento de Medicina, Spain.
We studied the nature of blast cells in 41 patients with acute leukemia
following a previous primary myelodysplastic syndrome (MDS) by a combined
multiparameter analysis including morphologic, immunophenotypic, and
molecular genetic (Igs, T-cell receptor (TCR)- beta, -gamma, and -delta and
the major breakpoint cluster region [M- bcr]) investigations. In addition,
the clinical and hematologic characteristics according to the
immunophenotype of blast cells were analyzed. Our results show that,
although the granulocytic and/or monocytic lineages are those most commonly
involved in these acute leukemias, other cell components, including the
megakaryocytic and lymphoid, may be present (12% and 15% of the cases,
respectively). Moreover, both morphologic and phenotypic studies show the
frequent coexistence of two or three cell populations. Interestingly, in
all cases the lymphoblastic component constantly displayed an early B
phenotype (CD19+, CD10-, TdT+). Upon analyzing whether the type of MDS
conditioned any differences in the immunophenotype of blast cells, we
observed that, although the lymphoid lineage may be involved in all MDS
subgroups, some differences emerge within the myeloid leukemic
transformations. Thus, the refractory anemias with excess of blasts (RAEB)
and RAEB in transformation displayed a significantly higher incidence of
myeloblastic and megakaryoblastic transformations, while in the RA, RA with
ring sideroblasts and chronic myelomonocytic leukemia, the
granulo-monocytic phenotype predominated. In addition, our results show
that the clinical and hematologic characteristics of these patients may be
partially related to the immunophenotype of the blast cells. Ig heavy chain
gene rearrangements were found in two of 19 patients analyzed (11%), one
with a hybrid leukemia (lymphoid-myeloid) and the other with a
granulo-monocytic phenotype. Two other hybrid transformations analyzed were
in germline configuration. Gamma and delta gene rearrangements were found
in 21% and 37% of these acute transformation, respectively. The TCR-beta
and M-bcr were in germline configuration in all 19 cases studied. In
summary, immunophenotype and molecular studies point to a pluripotent stem
cell with preferential myeloid commitment as the target cell of leukemias
following a primary MDS.
Volume 78,
Issue 3,
pp. 768-774,
08/01/1991
Copyright © 1991 by The American Society of Hematology
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