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Blood, 15 June 2002, Vol. 99, No. 12, pp. 4634-4637
BRIEF REPORT
Human acute stem cell leukemia with multilineage differentiation
potential via cascade activation of growth factor receptors
Ugo Testa,
Giovanni F. Torelli,
Roberta Riccioni,
Andrea Onetti Muta,
Stefania Militi,
Luciana Annino,
Gualtiero Mariani,
Anna Guarini,
Sabina Chiaretti,
Jerome Ritz,
Franco Mandelli,
Cesare Peschle, and
Robin Foa
From the Department of Hematology-Oncology, Istituto
Superiore di Sanità, Rome, Italy; the Department of Cellular
Biotechnologies and Hematology and the Department of Experimental
Medicine and Pathology, University of Rome La Sapienza, Italy; the
Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard
Medical School, Boston, MA; and the Kimmel Cancer Institute, Thomas
Jefferson University, Philadelphia, PA.
The morphologic, immunophenotypic, genotypic, genomic, and
functional features of an undifferentiated acute leukemia with stem
cell features are reported. At light and electron microscopy, the
leukemic population was represented by primitive progenitor cells with
no evidence of differentiation. The blasts were CD34+,
AC133+, CD71 , HLA-DR,
CD38/dim+, CD90+, CD117dim+,
flt3+; did not express B, T, or myeloid-associated
antigens; and showed a germline configuration of the immunoglobulin and
T-cell receptor. Genomic profiling documented the expression of
early stem cell and myeloid-associated genes. Receptors for
early-acting hemopoietic growth factors (HGFs) were detected, while
receptors for unilineage HGF were not expressed. Incubation with the
flt3 or Kit ligand induced the expression of unilineage HGF receptors,
allowing these cells to respond to their respective ligands. Growth
without differentiation was sustained only in the presence of
early-acting HGF, namely flt3 ligand, while early and unilineage HGF
gave rise to all types of hemopoietic colonies.
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