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)

Originally described by Dameshek in 1951, myeloproliferative disorders are today classified as myeloproliferative Neoplasms (MPNs) in WHO's Classification of Tumors of Hematopoietic and Lymphoid Tissues. The term includes a range of conditions, [ie, BCR-ABL-positive chronic myelogenous leukemia (CML), chronic neutrophilic leukemia (CNL), polycythemia vera (PV), primary myelofibrosis (PMF), essential thromobocythemia (ET), chronic eosinophilic leukemia not otherwise specified (CEL-NOS), mastocytosis, and unclassifiable myeloproliferative neoplasm]. In the specific case of CML, a better understanding of the pathogenesis and pathophysiology of the disease has led to a targeted therapy. The presence of chromosome Philadelphia, t(9;22)(q34;11) results in the oncogene BCR-ABL, which characterizes the disease; this molecular rearrangement gives rise to a tyrosine-kinase, which in turn triggers the proliferation of the myeloid line through the activation of the signaling pathways downstream. Tyrosine-kinase inhibitors (TKIs) have altered the therapy and monitoring of CML patients and improved both their prognosis and quality of life. In 2005, various groups of investigators described a new point mutation of the gene JAK2 associated to MPNs. Although the presence of this mutation has led to a modification in the diagnostic criteria of these conditions, the impact of the use of JAK2 inhibitors on the prognosis and course of the disease continues to be controversial.
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PMID:Jak-2 positive myeloproliferative neoplasms. 2462 6

The FIP1L1-PDGFRA rearrangement results in constitutive activation of the tyrosine kinase PDGFRA. Neoplasms harboring this rearrangement are responsive to imatinib mesylate at doses much lower than those recommended for the treatment of chronic myelogenous leukemia. Only a single report has described the identification of FIP1L1-PDGFRA in chronic myelomonocytic leukemia (CMML). Herein, we present a case report of a patient in whom the FIP1L1-PDGFRA was discovered as he evolved from CMML to acute myeloid leukemia (AML). The presence of a dominant neoplastic clone with FIP1L1-PDGFRA rearrangement was suspected on the basis of sudden onset of peripheral and bone marrow eosinophilia and confirmed by fluorescence in situ hybridization and molecular diagnostic tests. Whereas the patient was initially refractory to chemotherapy before the rearrangement was detected, subsequent therapy with imatinib led to complete remission.
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PMID:Discovery of imatinib-responsive FIP1L1-PDGFRA mutation during refractory acute myeloid leukemia transformation of chronic myelomonocytic leukemia. 2466 61

Based on the current WHO Classification of Myeloid Neoplasms, cytogenetic findings play a central role in the diagnostic classification of the myeloid malignancies. Cytogenetic abnormalities detected at primary diagnosis may change over time. Karyotype changes can be characterized as cytogenetic evolution, cytogenetic regression or a combination of both. While the exact mechanism of cytogenetic evolution is not completely understood, the process of cytogenetic evolution is not random, but follows different, and often disease-specific patterns during progression and relapse of myeloid neoplasms. Important lessons were learned from the cytogenetic evolution pathways observed over the course of chronic myelogenous leukemia (CML), progressing through chronic phase into accelerated phase and blast crisis. Cytogenetic evolution pathways of CML are divided into major and minor route abnormalities. The major route changes include an extra Ph chromosome (+Ph) trisomy 8 (+8) and the occurrence of an i(17q). The six most common minor route abnormalities include -7, -17, +17, +21 and -Y and one structural change, t(3;21). Recently an increased number of CML cases with karyotype abnormalities in Ph-negative cells have been reported in patients treated with imatinib. These abnormalities include trisomy 8, abnormalities of chromosome 7, and chromosome 20. The significance of the Ph-negative karyotype changes in subsequent development of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) is unclear. Nevertheless, the occurrence of clonal abnormalities in Ph-negative cells underlines the importance of conventional cytogenetic studies in monitoring of CML patients. In AML, karyotype changes commonly occur between diagnosis and relapse status post chemotherapy. Karyotype evolution seems more common in patients who had unfavorable aberrations at diagnosis as compared to patients with favorable or intermediate abnormalities. Karyotype evolution results in shortened remission duration as compared to cases without cytogenetic change. Recent studies on cytogenetic evolution at relapse after allogeneic hematopoietic cell transplantation (allo-HCT) were similar to the data observed in chemotherapy-treated AML. Serial bone marrow evaluations after allo-HCT offer insights into the dynamics of karyotype evolution, notably, they demonstrated that a detection of karyotype abnormalities is usually followed by a relapse within the next 90 days. As a contrast, karyotype abnormalities were not observed in patients who do not relapse in the next 3 months. CGE at relapse was associated with significantly decreased postrelapse and post-transplantation survival compared with the non-CGE group. Very few data exist regarding a potential association between the dose or certain types of chemotherapy and cytogenetic evolution. Based on the results of a single study conducted recently, no specific chemotherapy regimen emerged to predispose for cytogenetic evolution. Further studies are necessary to evaluate the impact of the altered bone marrow environment and immunosuppression on karyotype stability.
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PMID:Relapse and cytogenetic evolution in myeloid neoplasms. 2914 72