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Prethymic phenotype and genotype of pre-T (CD7+/ER-)-cell leukemia and its
clinical significance within adult acute lymphoblastic leukemia [see
comments]
E Thiel, BR Kranz, A Raghavachar, CR Bartram, H Loffler, D Messerer, A Ganser, WD Ludwig, T Buchner and D Hoelzer
Department of Hematology and Oncology, Free University of Berlin, FRG.
Pretreatment blast cells from 739 adults with acute lymphoblastic leukemia
(ALL) were immunophenotyped as part of a prospective treatment protocol
study. Among 192 patients (26%) with T lineage ALL, 47 (6%; 24% of T
lineage ALL) had lymphoblasts without sheep erythrocyte rosette formation,
but with pan-T antigen CD7 on the membrane and intracellular CD3 proteins
mostly in perinuclear accumulation. The T- cell surface antigens CD5 and/or
CD2 and focal acid phosphatase were additional markers of this subgroup
traditionally called pre-T ALL, whereas thymocyte antigen CD1 as well as
CD4 and CD8 antigens were not expressed. Hematopoietic progenitor cell
markers, namely terminal deoxynucleotidyl transferase (TdT), and in part
common ALL antigen (CD10), HLA-DR antigens, and/or My-10 (CD34), a unique
antigen of marrow cells absent in thymus cells, further characterized this
immature T-ALL form of putative prothymocytic phenotype (CD7+/intracellular
CD3+/TdT+/My-10+/-/HLA-DR+/-/CD10+/-). The prethymic T cell character was
supported by germ-line T-cell receptor beta genes found in 21 of 36
patients analyzed. In five cases only T gamma-chain genes were rearranged.
Fifteen patients, however, had rearrangements of both T beta and T gamma
genes. Immunoglobulin heavy chain genes were rearranged only in two cases.
Pre-T ALL differed significantly from E-rosette+ T-ALL in some presenting
clinical features, namely mediastinal mass, lymphoadenopathy, and platelet
count, and independently of clinical factors in prognosis (P = .02, median
remission duration: 15.7 v 33.5 months, and P = .02, median survival time:
24.6 v 50.7 months). We conclude that ALL classification based solely on T-
or B-cell lineage affiliation is not sufficient but needs further
subdivision according to relevant maturation stages as exemplified here
within the T-cell axis. The putative prethymic T cell progenitor phenotype
described might help elucidate the sequence of genetic events that commit
normal hematopoietic cells to the T-cell lineage.
Volume 73,
Issue 5,
pp. 1247-1258,
04/01/1989
Copyright © 1989 by The American Society of Hematology
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