Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report an interesting case of Malignant Histiocytosis (MH) with polyploid clones characterized by i(17q) and t(9; 22) translocation. A 47-year-old man had lymphadenopthy, splenomegaly and leukopenia at presentation. Bone marrow (BM) cytology showed 10.5% abnormal histiocytes. Karyotypic analyses with R- and G-banding techniques on BM cells revealed complex abnormalities: 88, XXYY, add(2) (p25), -4, -8, -11, i(17q), -21[4]/89, idem, t(9; 22) (q34; q11), +22[26]/46, XY [47], of which, t(9; 22) was confirmed by fluorescence in situ hybridization using a chromosome 22 paint wcp 22+. This patient was treated with interferon-alpha and COP regimen. 10 months later he achieved a complete hematologic and cytogenetic remission (CR). However, relapse occurred one year after achieving CR. At that time, cytogenetic examination showed a new polyploid clone characterized by add(1) (p36), add(2) (p25), -4, -8, t(9; 22), -11, i(17q), -21, +22 in addition to the other two polyploid clones observed previously. RT-PCR indicated that the BCR/ABL transcript (165bp) observed in classic chronic myeloid leukemia, was present, MH with t(9; 22) has not previously been described in the literature. This case may be the first one of MH with t(9; 22), and is likely a secondary event.
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PMID:A Case of Malignant Histiocytosis having Polyploid Clones Characterized by an Isochromosome of the Long Arm of Chromosome 17 [i(17q)] and t(9;22) Translocation. 2740 5

Primary myelofibrosis (PMF) is one of the BCR/ABL-negative myeloproliferative neoplasms (MPNs), characterized by the diffuse fibrous hyperproliferation, bone marrow osteosclerosis, extramedullary hematopoiesis, and marked splenomegaly. The patients with PMF have an insidious onset, a long duration of clinical course, and the deteriorated quality of life. It has been reported that the CALR gene 9 exon mutations were detected in 25-30% PMF patients, particularly as high as 80% in the JAK2/MPL-negative ones. As the second most common mutation in BCR/ABL-negative MPNs, CALR mutation has been included in the latest World Health Organization (WHO) classification criteria as one of the main diagnostic criteria for both essential thrombocythemia (ET) and PMF. Moreover, the CALR mutations indicated a favorable prognosis, which the mechanism is still under investigation. It was demonstrated that a characterized high expression of EZH2 and SUZ12 in CALR-mutated patients. Taking EZH2 as the research entry point, we initially discussed the mechanism that the CALR-positive patients with PMF exhibited a better prognosis in the current study.
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PMID:Elevated expression of the EZH2 gene in CALR-mutated patients with primary myelofibrosis. 2956 May 22

Introduction: The abnormally activated JAK-STAT pathway plays a central role in the pathogenesis of BCR/ABL-negative myeloproliferative neoplasms (MPNs), simultaneously providing a theoretical and clinical basis for the development of small-molecule compounds targeting JAK. The first approved drug, ruxolitinib, demonstrated a rapid and durable improvement of symptoms and splenomegaly accompanied with better overall survival in myelofibrosis (MF) patients. However, ruxolitinib-related adverse effects and resistance are limitations, so there is an urgent need to develop new JAK inhibitors to retain the efficacy of ruxolitinib and avoid its deficiency. Areas covered: This review discusses the preclinical and clinical studies of momelotinib (MMB) aiming to gain a deeper understanding of the advantages and clinical limitations of this drug. Expert opinion: The clinical trial data available thus far indicate that MMB is not inferior to ruxolitinib in spleen response and symptoms response, with the improvement of anemia surprising. The only obstacle that may slowdown its approval is treatment-emerged peripheral neuropathy (PN). If we can minimize MMB's treatment-related PN by administration optimization, MMB promises to be a good choice of individualized treatment for MF patients mainly manifesting as anemia.
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PMID:Momelotinib for the treatment of myelofibrosis. 3145 Sep 73

Rare chronic myelogenous leukemia (CML) patients manifested as the primary blast phase without a chronic and accelerated phase. The occurrence of a t(8;21) translocation in secondary blast phase of CML or Philadelphia chromosome positive acute myelogenous leukemia (Ph+ AML) has been reported previously. No case of primary blast phase of chronic myelogenous leukemia (CML-BP) bearing one clone with t(9;22) and t(8;21) simultaneously has been reported. One Chinese patient presenting with extensive spontaneous ecchymosis and enlarged spleen diagnosed as acute myelogenous leukemia (AML) by smear and immunophenotype was given chemotherapy including daunorubicin 3 days and cytarabine 7 days without a tyrosine kinase inhibitor (TKI) drug at the beginning. Fresh frozen plasma and 4-factor prothrombin complex concentrate was also transfused for coagulation disorder. However, fusion genes BCR/ABL p210 and AML1/ETO were both positive and karyotype analysis showed the abnormalities of t(9;22) and t(8;21) in the same clones. Bone marrow aspirate on 7th day of chemotherapy indicated hypocellularity with 45% blasts remaining. Cytarabine was prolonged to nine days combined with imatinib 600 mg per day. His bone marrow aspirate after complete remission revealed t(8;21) clones disappearing, especially FISH of bone marrow smear detecting the BCR/ABL fusion signals in the basophilic erythroblasts, which confirmed his diagnosis as primary blast phase of CML rather than Ph+ AML. Thus, we report for the first time one patient diagnosed as primary blast phase of CML presenting with t(9;22) and t(8;21) simultaneously.
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PMID:Co-existence of t(9;22) and t(8;21) in primary blast phase of chronic myelogenous leukemia: clinical experience and literature review. 3193 3


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