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)

A somatic mutation that leads to activation of the JAK2 tyrosine kinase has recently been identified as a recurrent genetic abnormality in several different myeloproliferative disorders. A translocation generating the constitutively activated fusion protein PCM1-JAK2 has also been recently found in atypical chronic myelogenous leukemia and acute leukemia. This recent spate of independent studies (one of which is published in this issue of Oncogene) establish abnormal JAK2 activation as the underlying defect in a significant number of cases of myeloproliferative disease, and JAK2 as an important new therapeutic target.
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PMID:JAK the trigger. 1609 53

The rare recurrent translocation of (8;9)(p22;p24) with PCM1-JAK2 fusion was recently characterized in diverse hematological malignancies. Most of them are atypical chronic myeloid leukemia (CML) or other myeloproliferative disorders (MPD), and are predominantly in the male. We report a female patient with acute myeloid leukemia (AML) initially presenting with normal karyotype and negative HLA-DR expression who achieved complete remission after standard chemotherapy. The disease relapsed 7 months later with cytogenetic change of t(8;9)(p22;p24). Flow cytometry analysis showed evolutional change of immunophenotype from negative to positive HLA-DR expression and fluorescence in situ hybridization (FISH) analysis demonstrated a PCM1-JAK2 fusion gene. We speculate that the cytogenetic change of t(8;9)(p22;p24) may induce HLA-DR immunophenotypic switch and a coordination of the two evolutional changes may play a role in leukemic cell progression.
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PMID:Evolutional change of karyotype with t(8;9)(p22;p24) and HLA-DR immunophenotype in relapsed acute myeloid leukemia. 1859 80

Chronic myeloid leukemia (CML) is defined for many years as BCR-ABL1 positive disease, but older publications refer to a poor prognosis, clinically heterogeneous entity termed 'BCR-ABL1 negative CML' constituting about 5% of CML cases. Apart from very rare CML cases with cytogenetically cryptic, atypical variant BCR-ABL1 fusions that had been inadvertently missed during the diagnostic work up, most of these cases would now be classified as a subtype of myelodysplastic/myeloproliferative neoplasm (MDS/MPN), such as atypical CML (aCML), chronic myelomonocytic leukemia (CMML), or chronic neutrophilic leukemia (CNL). A minority would be classified as systemic mastocytosis with associated hematological neoplasm (SM-AHN), myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or with PCM1-JAK2 (MLN-eo), or chronic eosinophilic leukemia not otherwise specified (CEL-NOS).1.
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PMID:Update on CML-Like Disorders. 3286 48