Defective in vitro growth of primitive hematopoietic cells from pediatric patients with acute myeloid leukemia.
BACKGROUND
Acute myeloid leukemia (AML) is a neoplastic hematologic disorder that arises at the level of a primitive stem/progenitor cell. Most studies on the biology of the hematopoietic system in AML have focused on cells from adult patients; much less is known about hematopoietic cells from childhood AML.


METHODS
By using a negative immunoselection system, we have obtained a primitive cell population (enriched for CD34(+) Lin(-) cells) from the bone marrow (BM) of 17 pediatric AML patients and characterized its proliferation, expansion, and differentiation potentials in liquid cultures supplemented with a mixture of 8 different recombinant stimulatory cytokines.


RESULTS
The proportion of CD34(+) cells in AML patients was extremely heterogeneous, ranging from 0% to 74%. Regardless of their CD34(+) cell content, and in contrast to normal cells, AML cells showed a deficient capacity to proliferate even in the presence of the stimulatory cytokines. AML progenitors were unable to generate new progenitor cells, indicating their inability to expand. Interestingly, AML cells were able to differentiate in culture, giving rise to morphologically recognizable precursors. A major difference, however, as compared to hematopoietic progenitors from normal subjects, was the fact that whereas in cultures of normal cells both myeloid and erythroid precursors were produced, in AML cultures the vast majority of the cells generated corresponded to myeloid cells, mostly mature macrophages.


CONCLUSIONS
As compared to their normal counterparts, primitive hematopoietic cells from pediatric patients with AML possess impaired proliferation, expansion, and differentiation potentials in vitro.
Dorantes-Acosta
Elisa
E
Oncology Research Unit, Oncology Hospital, National Medical Center, IMSS, Mexico City, Mexico.
Chávez-González
Antonieta
A
Santos
José Ignacio
JI
Medina-Sanson
Aurora
A
Mayani
Hector
H
D000293:Adolescent; D018952:Antigens, CD34 / Q000097:blood; D001854:Bone Marrow Cells / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006412:Hematopoietic Stem Cells / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000378:metabolism / Q000473:pathology; D008297:Male
D018952:Antigens, CD34; D016207:Cytokines