Clonal variation in the B-lineage acute lymphoblastic leukemia response to multiple cytokines and bone marrow stromal cells.

Abstract

The acquisition of genetic abnormalities in human B-lineage acute lymphoblastic leukemia (ALL) culminates in the clonal expansion of bone marrow (BM)-derived leukemic blasts. However, the response of leukemic cells to signals transduced by the BM microenvironment is not completely understood. The present study describes a new human B-lineage ALL cell line designated BLIN-4 (B LINeage-4). BLIN-4 cells respond to multiple cytokines/human BM stromal cell-derived molecules. One subline (BLIN-4E) undergoes cell death in the absence of BM stromal cells or cytokines and slowly proliferates on human BM stromal cells supplemented with interleukin (IL)-7 + FLT3-ligand. Another subline (BLIN-4L) slowly proliferates in the absence of cytokines and BM stromal cells and shows robust proliferation on BM stromal cells supplemented with IL-7 + FLT3-ligand. Although human BM stromal cells are comparable with IL-7 + FLT3-ligand in supporting proliferation of BLIN-4L cells, neutralizing antibody experiments demonstrate that BLIN-4L expansion on BM stromal cells is IL-7/FLT3-ligand independent. BLIN-4L could also respond to human thymic stromal lymphopoietin. BLIN-4E and BLIN-4L have the identical immunoglobulin heavy chain rearrangement and a CD10(+)/CD19(+)/CD20(-)/CD22(+)/CD40(+)/mu heavy chain(-) phenotype. The original BM leukemic blasts harbored a ring chromosome 4 with a low percentage of cells also having either trisomy 8 or trisomy 18. The BLIN-4 sublines maintained the ring chromosome 4, but the trisomy 8 and trisomy 18 segregated into BLIN-4E and BLIN-4L, respectively. Thus, the BLIN-4 sublines exhibit biological characteristics consistent with a potential evolution in B-lineage ALL involving subclones with decreasing requirements on the BM microenvironment.

• Authors: N Shah, L Oseth, H Tran, B Hirsch, T W LeBien
• Journal: Cancer research (Cancer Res) Vol. 61 Issue 13 Pg. 5268-74 (Jul 01 2001) ISSN: 0008-5472 [Print] United States
• PMID: 11431369 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Culture Media, Conditioned
• Cytokines
• Interleukin-7
• Membrane Proteins
• Proto-Oncogene Proteins
• Receptors, Interleukin-7
• flt3 ligand protein
• FLT3 protein, human
• Receptor Protein-Tyrosine Kinases
• fms-Like Tyrosine Kinase 3
• Thymic Stromal Lymphopoietin

Topics

• Adolescent
• Bone Marrow Cells (cytology, metabolism)
• Burkitt Lymphoma (genetics, pathology)
• Cell Division (drug effects)
• Cell Lineage
• Cell Survival (drug effects)
• Clone Cells
• Culture Media, Conditioned
• Cytokines (pharmacology)
• Female
• Humans
• Interleukin-7 (pharmacology)
• Membrane Proteins (pharmacology)
• Proto-Oncogene Proteins (biosynthesis)
• Receptor Protein-Tyrosine Kinases (biosynthesis)
• Receptors, Interleukin-7 (biosynthesis)
• Stromal Cells (metabolism)
• Tumor Cells, Cultured
• fms-Like Tyrosine Kinase 3
• Thymic Stromal Lymphopoietin