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Long-term culture of primary human lymphoblastic leukemia cells in the absence of serum or hematopoietic growth factors.

Abstract：

OBJECTIVE:B-lineage acute lymphoblastic leukemia (ALL) and chronic myeloid leukemia in lymphatic blastic phase in adults have poor prognoses despite intensive chemotherapy. Novel targeted treatment modalities emerge, but their evaluation requires relevant in vitro models of lymphoblastic leukemia. Presently available cell lines do not fully represent this heterogeneous disease. Available in vitro culturing protocols do not support long-term proliferation of primary cells. We therefore aimed to develop a culture system that allows long-term proliferation of primary human B-lineage lymphoblastic leukemia. MATERIALS AND METHODS:Primary lymphoblastic leukemia cells were cultured in a defined serum-free medium, in the absence or presence of human hematopoietic growth factors or serum. RESULTS:In the defined serum-free medium, cells from 12 of 34 cases immediately proliferated in vitro. In the absence of hematopoietic growth factors and serum these cases proliferated for more than 1 year without signs of exhaustion. The culturing system supported different subtypes of lymphoblastic leukemia. Two chronic myeloid leukemia in lymphatic blastic phase, four bcr/abl-positive ALL, one etv6/abl-positive ALL, 2 e2a-pbx1-positive ALL, and one t(9;11)-positive ALL could be long-term expanded, as well as two ALL that displayed nontypical cytogenetics. Not all bcr/abl- or e2a-pbx1-positive ALL proliferated in vitro, demonstrating heterogeneity within these subtypes. The proliferating bcr/abl- and etv6/abl-positive cells displayed sensitivity to imatinib, demonstrating that their proliferation depended on the activity of these oncoproteins. CONCLUSION:The serum-free culturing system may be a valuable instrument in the study of ALL cell biology, as well as in the evaluation of novel targeted therapeutics.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Nijmeijer BA,Szuhai K,Goselink HM,van Schie ML,van der Burg M,de Jong D,Marijt EW,Ottmann OG,Willemze R,Falkenburg JH

doi

10.1016/j.exphem.2008.11.002

subject

Has Abstract

pub_date

2009-03-01 00:00:00

pages

376-85

issue

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(08)00520-1

journal_volume

pub_type

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Long-term culture of primary human lymphoblastic leukemia cells in the absence of serum or hematopoietic growth factors.