Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proto-oncogene, c-kit, encodes a transmembrane tyrosine kinase receptor (KIT) and plays an important role in haemopoiesis. We have identified a 95 kD soluble form of KIT (S-KIT) in culture supernatant of human megakaryoblastic cell line, CMK. To study the physiological significance of S-KIT, we have established a sensitive sandwich ELISA system. Serum samples from healthy individuals contained detectable amounts of S-KIT. Next, we determined a total of 220 samples from 134 patients with haemopoietic disorders. A considerable number of patients with acute myeloid leukaemia (AML), especially those with more immature phenotypes (M0, M1 or M2) had elevated levels of serum S-KIT. Those levels decreased to the normal range after effective chemotherapy. In chronic myeloid leukaemia, patients with myeloid blastic crisis showed markedly elevated levels of serum S-KIT. In contrast, S-KIT levels decreased in cases with either acute or chronic lymphoid leukaemia. There was a tendency for patients with severe aplastic anaemia to show decreased levels, but it was not significant. In myelodysplastic syndrome, S-KIT levels appeared to vary by subsets, with higher concentration in more advanced forms of the disease. Although the functional role of S-KIT is not yet elucidated, these results suggest that the serum S-KIT levels may reflect the pathological states of various haematological disorders.
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PMID:Soluble c-kit molecule in serum from healthy individuals and patients with haemopoietic disorders. 757 39

Flt3 ligand (flt3L) is a member of a small family of cytokines acting as tyrosine kinase receptor ligands that stimulate the proliferation of primitive hematopoietic progenitors in vitro. To gain insight into the physiological role of flt3L in early hematopoiesis, levels of flt3L were determined in serum of patients with multilineage bone marrow failure and related to the severity of stem cell depletion. In patients with aplastic anemia (AA) and in cancer patients with chemotherapy-induced transient suppression of hematopoiesis, flt3L fluctuated in an inverse relationship to the degree of bone marrow failure. In severe AA at diagnosis, levels of circulating soluble flt3L were highly elevated (2,653 +/- 353 pg/mL) as compared with normal blood serum values of 14 +/- 39 pg/mL. Flt3L returned to near normal levels within the first 3 months following successful bone marrow transplantation and in autologous remission induced by immunosuppressive therapy with antilymphocyte globulin (ALG; 100 +/- 31 and 183 +/- 14 pg/mL, respectively). In contrast, rejection of the graft or relapse of the disease after ALG was accompanied by an increase to high pretreatment concentrations of the circulating cytokine (3,770 +/- 2,485 and 1,788 +/- 233 pg/mL, respectively). Flt3L in serum inversely correlated with the colony-forming ability of AA bone marrow precursors in vitro (R = -.86), indicating that the concentration of the ligand reflects hematopoiesis at the progenitor cell level. Flt3L increased to 2,500 pg/mL in the serum of leukemia patients during chemoradiotherapy-induced bone marrow suppression and returned to normal values along with hematopoietic recovery. Expression of the membrane-bound form of flt3L was significantly elevated in mononuclear bone marrow and peripheral blood cells from patients with severe pancytopenia, suggesting de novo synthesis of the factor in response to bone marrow failure. The data provide a strong argument for the involvement of flt3L in the regulation of early hematopoiesis in vivo.
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PMID:Flt3 ligand level reflects hematopoietic progenitor cell function in aplastic anemia and chemotherapy-induced bone marrow aplasia. 897 41