Human granulocyte-macrophage colony-stimulating factor supports the clonogenic growth of B-lineage acute lymphoblastic leukemias expressing myeloid antigens.
The effects of granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-6 on clonogenic growth of blast-cell progenitors from 19 immunologically defined CD10-positive B-lineage acute lymphoblastic leukemias (ALL) coexpressing (My+ALLs) or not (My-ALLs) myeloid antigens have been studied. Our results demonstrate that GM-CSF was able to support the clonogenic growth of blast cells from My+ALLs, being totally ineffective on My-All samples. Accordingly, both alpha and beta chains of GM-CSF receptor (R) were expressed by My+ALL blasts, as investigated by reverse-transcriptase polymerase chain reaction (RT-PCR). Colony cells from GM-CSF-stimulated My+ALL cultures displayed the same immunophenotype as primary leukemic cells at diagnosis (CD10+, CD19+, CD22+), and retained the expression of myeloid-associated antigens and of GM-CSF-R transcripts. Moreover, My+ALL blasts showed a preferential sensitivity to the growth-promoting activity of IL-3 and IL-6, as compared with My-ALL cells. In addition to rearrangements of the JH region of immunoglobulin genes, My+ALL cells showed aberrant rearrangements of gamma (three cases) and beta (two cases) T-cell receptor genes, as well as of bcr sequences (three cases). Our data, showing an unexpected cross-lineage response of My+ALLs to GM-CSF, and their preferential stimulation by IL-3 and IL-6, as compared with My-ALLs, further support the concept that My+ALLs represent a separate entity with unique biological features.
Gattei
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V
Unità Operativa Leucemie e Trapianto di Midollo, IRCCS, Aviano, Italy. vgattei@ets.it
Aldinucci
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D
Attadia
V
V
Degan
M
M
Alosi
M S
MS
De Iuliis
A
A
Babare
R
R
Rossi
F M
FM
Rupolo
M
M
Zagonel
V
V
Pinto
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A
D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology*; D002455:Cell Division; D002675:Child, Preschool; D002999:Clone Cells / Q000187:drug effects; D005260:Female; D015321:Gene Rearrangement; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D016130:Immunophenotyping; D007378:Interleukins / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000032:analysis / Q000235:genetics; D013234:Stem Cells / Q000276:immunology / Q000473:pathology
D015703:Antigens, CD; D007378:Interleukins; D012333:RNA, Messenger; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D016178:Granulocyte-Macrophage Colony-Stimulating Factor