Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is likely that leukemia results, at least in part, from mutations that lead to a block in the normal process of differentiation. A defined region of the cytoplasmic domain of the granulocyte colony-stimulating factor receptor (G-CSF-R) transmits signals for maturation or differentiation of myeloid progenitor cells. Mutations in this region have been found in some patients with severe congenital neutropenia (SCN) who subsequently evolved to acute myeloid leukemia (AML). To determine if mutations of the G-CSF-R are more widespread in hematological malignancies, we have investigated a total of 47 patients, including 29 patients with blast crisis of chronic myeloid leukemia (CML-BC) and 18 patients with de novo acute leukemia as well as 19 normal controls, by RT-PCR and SSCP analysis. Two point mutations were found in a single individual with secondary AML (FAB type M1). The first was heterozygous and is predicted to replace the normal glutamine at position 718 with a stop codon, leading to a truncated protein. An identical mutation has been described previously and shown to act in a dominant negative manner. The second mutation was homozygous and would substitute a lysine for the normal glutamic acid at position 785. No mutations were found in any other patient or control samples. We conclude that mutations in the cytoplasmic domain of the G-CSF-R are infrequent in CML-BC or acute leukemia but may contribute to malignant transformation in some cases.
 ...
PMID:Rarity of dominant-negative mutations of the G-CSF receptor in patients with blast crisis of chronic myeloid leukemia or de novo acute leukemia. 920 82

Between October 1995 and October 1998, 24 children aged 9 months to 17 years (median 11 years) underwent cytokine-mobilized allogeneic peripheral blood stem cell (PBSC) transplantation for treatment of hematological disorders. All of the transplants were the first allogeneic transplant for the recipient. Twenty patients were transplanted for hematological malignancies (ALL = 8, AML = 6, CML = 4, MDS = 2) and four patients were transplanted for non-malignant disease (thalassemia major = 2, Wiskott-Aldrich syndrome = 1, Kostmann's syndrome = 1). Nineteen donors were HLA-identical siblings, four were HLA-matched or single antigen mismatched parents, and one was a syngeneic transplant. Donors aged 8 to 38 years (median 15 years, 14 donors <18 years) received G-CSF 10 microg/kg/day subcutaneously beginning 4 days before PBSC collection and were submitted to one to three leukapheresis collections. The median CD34+ cell yield was 7.8 x 106 cells/kg recipient body weight. All patients achieved an ANC >0.5 x 109/l after a median of 13 days (range 10-21). Twenty-three patients eventually achieved platelet transfusion independence. One patient died on day 63 without ever achieving platelet transfusion independence. Four patients received platelet transfusions to maintain a platelet count well above 20 x 109/l due to bleeding complications. Of the 19 evaluable patients, the median time to a non-transfused platelet count of 20 x 109/l was 12 days (range 0-44). Ten of 23 at-risk patients developed acute GVHD grades II to IV, with grades III to IV in four patients. Twelve of 19 patients followed for at least 100 days have developed chronic GVHD (extensive = 2, limited = 10) with an actuarial risk of chronic GVHD of 75% at 1 year. The Kaplan-Meier estimate of event-free survival is 65% at 2 years. Four patients died (GVHD = 3, VOD = 1), three patients relapsed, and one patient with thalassemia major had a late graft failure with autologous recovery. Based upon our experience, allogeneic PBSCT is safe for both pediatric donors and recipients and engraftment of neutrophils and platelets is rapid. Bone Marrow Transplantation (2000) 25, 13-18.
 ...
PMID:Cytokine-mobilized allogeneic peripheral blood stem cell transplants in children result in rapid engraftment and a high incidence of chronic GVHD. 1065 8