title: Human acute stem cell leukemia with multilineage differentiation potential via cascade activation of growth factor receptors.
abstract: 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(+), CD117(dim+), 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.
authors.affiliation: Department of Hematology-Oncology, Istituto Superiore di Sanità, Rome, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: Testa
authors.forename: Giovanni F
authors.initials: GF
authors.lastname: Torelli
authors.forename: Roberta
authors.initials: R
authors.lastname: Riccioni
authors.forename: Andrea Onetti
authors.initials: AO
authors.lastname: Muta
authors.forename: Stefania
authors.initials: S
authors.lastname: Militi
authors.forename: Luciana
authors.initials: L
authors.lastname: Annino
authors.forename: Gualtiero
authors.initials: G
authors.lastname: Mariani
authors.forename: Anna
authors.initials: A
authors.lastname: Guarini
authors.forename: Sabina
authors.initials: S
authors.lastname: Chiaretti
authors.forename: Jerome
authors.initials: J
authors.lastname: Ritz
authors.forename: Franco
authors.initials: F
authors.lastname: Mandelli
authors.forename: Cesare
authors.initials: C
authors.lastname: Peschle
authors.forename: Robin
authors.initials: R
authors.lastname: Foa
mesh_terms: D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation; D019070:Cell Lineage; D016172:DNA Fingerprinting; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008565:Membrane Proteins / Q000494:pharmacology; D016184:Receptors, Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D017978:Receptors, Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D016184:Receptors, Colony-Stimulating Factor; D017978:Receptors, Growth Factor; C084881:flt3 ligand protein