Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Severe congenital neutropenia (SCN; or Kostmann syndrome) is an autosomal recessive disorder characterized by a maturation arrest of myelopoiesis at the level of promyelocytes. Myeloid precursor cells from patients with SCN require pharmacological dosages of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF; Filgrastim; Amgen, Thousand Oaks, CA) to differentiate to normal neutrophils. Thus, it is hypothesized that the underlying defect responsible for SCN is based on an abnormal G-CSF-induced signal transduction pathway. Because JAK2, a nonreceptor tyrosine kinase, is involved in the signaling pathway of G-CSF, we examined the expression and activity of JAK2 in neutrophils from SCN patients during r-metHuG-CSF treatment. The immunoprecipitated JAK2 protein showed increased tyrosine phosphorylation in neutrophils from SCN patients as compared with that in neutrophils from healthy donors, suggesting that this kinase is activated. In vitro kinase assays of immunoprecipitated JAK2 confirmed that neutrophils from SCN patients show an increased autophosphorylation of JAK2 in comparison with that of neutrophils from healthy volunteers. These findings suggest that JAK2 is activated in SCN patients.
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PMID:The protein tyrosine kinase JAK2 is activated in neutrophils from patients with severe congenital neutropenia. 854 39

Following chemotherapy in chronic myeloid leukaemia (CML), some peripheral blood (PB) cells may be Philadelphia (Ph) chromosome negative. The BCR-ABL mRNA status of residual Ph+ progenitors is not known. We examined the BCR-ABL mRNA status of individual colony-forming-unit granulocyte-macrophage (CFU-GM) colonies derived from PB harvested following chemotherapy. Seven patients were treated with 200 mg/m2/day cytarabine and 20 mg/m2/day Idarubicin and followed by Lenograstim. PB collections commenced daily when the white blood cell count reached 0.6 x 10(9)/l and continued until at least 5 x 10(8)/kg nucleated cells were obtained. CD34+ cells, Ph status, and CFU-GM were estimated at each harvest. For each patient, up to 24 individual CFU-GM colonies were analysed for BCR-ABL status. Two cases were BCR-ABL negative on all colonies and completely Ph-, and another case was BCR-ABL positive in all colonies and completely Ph+. In contrast, in two patients all colonies were BCR-ABL negative, despite virtually complete Ph+ metaphases. The final assessible case had five of nine BCR-ABL negative colonies, despite 94% Ph+ metaphases. After chemotherapy priming, the PB may contain Ph+ CFU-GM that do not express BCR-ABL.
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PMID:Molecular status of individual CFU-GM colonies derived from chemotherapy-mobilised peripheral blood stem cells in chronic myeloid leukaemia. 908 69