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)

Fitness landscapes, which provide a unique perspective for viewing co-evolving cell populations, were used to study the evolution of CML and MDS. This led to several conclusions: (1) accelerated phase CML and RAEB/RAEBt are not specific disease entities. They represent the time when AML cells are replacing preleukemia cells; (2) monoclonal hemopoiesis and RA/RARS represent a variety of clinical syndromes with a common appearance but with different evolutionary potential; (3) malignant cells alter the fitness landscape enhancing their proliferative advantage. These studies provide the basis for new approaches to treatment.
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PMID:Fitness landscapes and the myeloid leukemias. 1007 Nov 32

Relapse is the major cause of death after allogeneic bone marrow transplantation (BMT). This study tested the hypothesis that the numbers of donor mononuclear cells, lymphocytes, and CD34(+) cells influence relapse and event-free survival (EFS) after BMT. The study population consisted of 113 consecutive patients with hematologic malignancies who underwent non-T-cell-depleted BMT from HLA-matched siblings. Sixty-four patients had low-risk diagnoses (ALL/AML CR1, MDS RA/RARS, and CML CP1); 49 patients had high-risk diagnoses (all others). CD34(+) cells, T cells, B cells, natural killer cells, monocytes, and a rare population of CD3(-), CD4(bright) cells in the allografts were measured by flow cytometry. The CD3(-), CD4(bright) cells in bone marrow had the same frequency and phenotype as CD123(bright) type 2 dendritic cell (DC) progenitors, and they differentiated into typical DCs after short-term culture. Cox regression analyses evaluated risk strata, age, gender, and the numbers of nucleated cells, CD3(+) T cells, CD34(+) hematopoietic cells, and CD4(bright) cells as covariates for EFS, relapse, and nonrelapse mortality. Recipients of larger numbers of CD4(bright) cells had significantly lower EFS, a lower incidence of chronic graft-versus-host disease (cGVHD), and an increased incidence of relapse. Recipients of larger numbers of CD34(+) cells had improved EFS; recipients of fewer CD34(+) cells had delayed hematopoietic engraftment and increased death from infections. In conclusion, the content of donor CD4(bright) cells was associated with decreased cGVHD and graft-versus-leukemia effects in recipients of allogeneic bone marrow transplantation, consistent with a role for donor DCs in determining immune responses after allogeneic BMT.
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PMID:Larger numbers of CD4(bright) dendritic cells in donor bone marrow are associated with increased relapse after allogeneic bone marrow transplantation. 1134 16

Myeloproliferative neoplasms (MPNs) and related chronic disorders constitute a subgroup of myeloid malignancies which are defined according to clinical, morphological and molecular features by the actual World Health Organization classification of tumors of the haematopietic system. Screening procedures for a BCR-ABL fusion gene, JAK2, thrombopoietin receptor and KIT mutations are formally included in the diagnostic approach. Myelodysplastic/MPN overlap syndromes include rare entities such as refractory anemia with ringed sideroblasts characterized by a high proportion of JAK2V617F mutated cases. The paradigm of targeted treatment of chronic myeloid leukemia with imatinib has now been extended to eosinophilia-associated myeloid neoplasms with PDGFRA, PDGFRB or FGFR1 gene mutations. Pegylated interferon-alpha has convincingly been proved to reduce the JAK2 allele burden. JAK2 inhibitor drugs are currently being tested in clinical trials. The development of pathogenesis-targeted diagnostic and therapeutic approaches to the various MPNs will continue in the future.
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PMID:[Chronic myeloid neoplasms. Diagnostic criteria and current therapeutic concepts]. 2007 59

Janus Kinase 2 (JAK2) is a member of a family of four Janus Kinases, 2, and 3 and tyrosine kinase 2. Mutated JAK2 (V617F) has the ability to activate downstream signal transducer and activator of transcription (STAT)-mediated transcription in the absence of the ligand erythropoietin. The autoinhibitory activity of JAK2 is disrupted by the presence of the V617F mutation. Somatic mutation in JAK2 (V617F) gene has been reported in myeloid disorders. This study reports the prevalence of JAK2V617F using amplification refractory mutation system (ARMS)-polymerase chain reaction in 246 Egyptian patients with different myeloid disorders and studied the relationship between the JAK2V617F mutation and parameters in peripheral blood. The mutation was detected among 88 patients (35.8%) with different myeloid disorders. JAK2V617F was found among 81.4% of polycythemia vera (PV), 50% of essential thrombocythemia, 46.1% of primary myelofibrosis (PMF), 33.3% of philadelphia (Ph)-negative chronic myeloid leukemia, 33.3% of myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN), and 50% of refractory anemia with ringed sideroblasts associated with marked thrombocytosis (RARS-T) patients. Hemoglobin and white blood cells were significantly higher in the mutated group of MPN including PV, essential thrombocythemia, and PMF, whereas platelet counts were higher among the mutated PV, PMF, RARS-T, and MDS/MPN group. The identification of JAK2V617F mutations has raised the prospect of developing specific JAK2V617F inhibitors to treat mutated patients.
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PMID:Acquired mutation of the tyrosine kinase JAK2V617F in Egyptian patients with myeloid disorders. 2103 66