C-kit receptors in childhood malignant lymphoblastic cells.
The product of the protooncogene c-kit is the receptor for the hematopoietic cytokine stem cell factor (SCF). C-kit is expressed on leukemic cells of the erythroid, myeloid, and mast-cell lineage and SCF has a proliferative effect on some of these cells. The role of SCF and c-kit in lymphoid malignancies is much less clear. Here we review the role of c-kit in normal lymphopoiesis and summarize its role in lymphoid malignancies. C-kit is expressed in normal lymphopoiesis and its ligand SCF synergizes with IL-7 to enhance the proliferation of B- and T-cell progenitors. In malignant lymphopoiesis, c-kit can also be expressed in B and T-lymphoblastic cells from children with non Hodgkin's lymphoma (NHL) or acute lymphoblastic leukemia (ALL) when analyzed by the highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR). While c-kit receptors were detected by flow cytometric (FCM) analysis on about 40% of fresh T-lymphoblastic biopsy tumor cell preparations or T-lymphoblastic cell lines, no receptors were detected on B-lymphoblastic fresh cells or cell lines from children with B-ALL or Burkitt's lymphoma (BL). Almost all of the lymphoblastic cells expressing c-kit protein responded to recombinant human (rh)SCF with a downregulation of c-kit receptors. A proliferative response was detected only in a minority of these cells. B-ALL or BL cell lines showed no response to rhSCF. Upregulation of c-kit in T-lymphoblastic cells could be demonstrated by the addition of IL-1 beta, TNF-alpha, TGF-beta or A23187, and downregulation by rhSCF or phorbol myristate acetate (PMA). Despite upregulation of c-kit mRNA, protein remained undetectable on B-ALL or BL cells in the presence of A23187. The metabolic state of the cells seemed to influence c-kit expression, since c-kit was upregulated in T-lymphoblastic cells by the addition of new medium. C-kit appears to play a role in the growth of some malignant T-lymphoblastic but not B-lymphoblastic cells.
Sykora
K W
KW
Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany.
Tomeczkowski
J
J
Reiter
A
A
D000818:Animals; D002051:Burkitt Lymphoma / Q000235:genetics; D002648:Child; D016207:Cytokines / Q000502:physiology; D015972:Gene Expression Regulation, Neoplastic; D006410:Hematopoiesis / Q000502:physiology; D006801:Humans; D007938:Leukemia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008214:Lymphocytes / Q000378:metabolism* / Q000473:pathology*; D008223:Lymphoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D051379:Mice; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000473:pathology; D019009:Proto-Oncogene Proteins c-kit / Q000502:physiology*; D019089:Stem Cell Factor / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit