c-kit Expression in human megakaryoblastic leukemia cell lines

• Published in: Blood 1994-04, Vol.83 (8), p.2133-2144
• Main Authors: ZHEN-BO WU, WEILI MA, UPHOFF, C. C, QUENTMEIER, H, DREXLER, H. G
• Format: Article
• Language: English
• Subjects: Apoptosis; Base Sequence; Biological and medical sciences; Cytokines - pharmacology; DNA - metabolism; Gene Expression; Hematologic and hematopoietic diseases; Humans; Immunophenotyping; Leukemia, Megakaryoblastic, Acute - genetics; Leukemia, Megakaryoblastic, Acute - immunology; Leukemia, Megakaryoblastic, Acute - pathology; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; Molecular Sequence Data; Polymerase Chain Reaction; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins c-kit; Proto-Oncogenes; Receptor Protein-Tyrosine Kinases - genetics; Receptors, Colony-Stimulating Factor - genetics; Tretinoin - pharmacology; Tumor Cells, Cultured
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.v83.8.2133.2133

A panel of 164 continuous human leukemia-lymphoma cell lines was analyzed for expression of c-kit using Northern blotting and reverse transcriptase-polymerase chain reaction (RT-PCR). The c-kit transcripts were detectable in cell lines assigned to the myeloid (in 7 of 29 by Northern blotting and in 4 of 8 by RT-PCR), monocytic (in 1 of 24 by Northern blotting and in 3 of 6 by RT-PCR), erythroid (in 6 of 8 by Northern blotting and in 5 of 5 by RT-PCR), and megakaryoblastic (in 10 of 10 by Northern blotting) lineages, c-kit expression was not seen by Northern blotting or RT-PCR analysis in any of the 93 lymphoid leukemia, myeloma, or lymphoma cell lines. Treatment of four megakaryoblastic cell lines with protein kinase C activators (phorbol ester 12-O-tetradecanoylphorbol 13-acetate and Bryostatin 1) led to terminal differentiation as assessed by morphologic alterations, changes in the surface marker profile, and growth arrest. These effects were associated with enhanced c-kit mRNA expression. Exposure to all-trans retinoic acid down-regulated c-kit mRNA levels, while simultaneously causing morphologic alterations in all four cell lines. Stimulation with growth factors (interleukin-3, granulocyte macrophage-colony stimulating factor, and insulin-like growth factors I and II), used to assess any role of c-kit in proliferative processes, did not lead to significant upregulation or downregulation of c-kit expression. The finding of constitutive and high expression of c-kit mRNA in all megakaryoblastic leukemia cell lines and its modulation by various reagents might further contribute to the understanding of megakaryopoietic proliferation, differentiation, and leukemogenesis.