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Phenotypic and molecular heterogeneity in Philadelphia chromosome- positive
acute leukemia
C Hirsch-Ginsberg, C Childs, KS Chang, M Beran, A Cork, J Reuben, EJ Freireich, LC Chang, FJ Bollum and J Trujillo
Department of Hematology, University of Texas, M.D. Anderson Hospital and
Tumor Institute, Houston 77030.
Philadelphia chromosome-positive (Ph1) acute leukemia is a heterogeneous
subset of acute leukemia with a poor prognosis. We studied five patients to
determine the potential for phenotypic and molecular heterogeneity.
Cellular characterization studies included light myeloperoxidase (L-MPO),
terminal deoxynucleotidyl transferase (TdT), ultrastructural MPO (U-MPO),
and immunophenotyping by flow cytometry using T11, T3, T4, T8, Leu 1, B1,
Leu 12, HLA-DR (la), CALLA (J5), OKM1, My4, My7, My8, My9, and My10. DNA
was analyzed for rearrangements of the breakpoint cluster region (bcr),
immunoglobulin heavy chain, joining region (JH), immunoglobulin kappa light
chain constant region (C kappa), and T cell receptor (TcR beta). RNA dot
blots were hybridized by using molecular probes for MPO and TdT. We found
that four of five cases were acute mixed-lineage leukemia (AMLL). One
patient had acute unclassifiable leukemia. Of the four patients classified
as having AMLL, three showed myeloid and lymphoid features, with one
patient showing myeloid, T cell, and B cell features. The last case showed
T cell and B cell features only. In one patient MPO/RNA was positive in
spite of insufficient L-MPO or U-MPO to diagnose acute myelogenous leukemia
(AML), thereby suggesting significant MPO gene expression before the
production of sufficient MPO protein to meet the French-American-British
criteria for AML. Three of the five patients showed rearrangement of bcr
(cases 1, 2, and 5). Studies of these five patients support the concepts of
molecular and phenotypic heterogeneity in Ph1 acute leukemia, demonstrate a
high incidence of AMLL in this subset of acute leukemia, and support the
use of lineage-associated molecular probes to define lineage at an earlier
stage than previously possible.
Volume 71,
Issue 1,
pp. 186-195,
01/01/1988
Copyright © 1988 by The American Society of Hematology

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