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

A 40-year-old male patient presented with leukocytosis and mild splenomegaly. Bone marrow aspirate showed myeloid hyperplasia and eosinophilia resembling chronic myelogenous leukemia in the chronic phase. Cytogenetic examination of bone marrow cells revealed an unusual karyotype, t(8;13)(p11;q12), in 20/20 metaphases. Not the BCR/ABL, but the ZNF198/FGFR1 chimeric mRNA was detected by reverse transcription-polymerase chain reaction. Since 1992, 12 patients with a similar atypical myeloproliferative disorder with T-cell non-Hodgkin's lymphoma or eosinophilia, associated with a t(8;13) translocation in both bone marrow and lymph node specimens, have been described. The present case is an additional one that should be classified into this new clinicopathologic entity.
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PMID:A chronic myelogenous leukemia-like myeloproliferative disorder accompanied by T-cell lymphoblastic lymphoma with chromosome translocation t(8;13)(p11;q12): a Japanese case. 1064 54

Constitutive activation of FGFR1, through rearrangement with various dimerization domains, leads to atypical myeloproliferative disorders where, although T cell lymphoma are common, the BCR-FGFR1 chimeric kinase results in CML-like leukemia. As with the human disease, mouse bone marrow transduction/transplantation with BCR-FGFR1 leads to CML-like myeloproliferation as well as B-cell leukemia/lymphoma. The murine disease described in this report is virtually identical to the human disease in that both showed bi-lineage involvement of myeloid and B-cells, splenomegaly, leukocytosis and bone marrow hypercellularity. A CD19(+) IgM(-) CD43(+) immunophenotype was seen both in primary tumors and two cell lines derived from these tumors. In all primary tumors, subpopulations of these CD19(+) IgM(-) CD43(+) were also either B220(+) or B220(-), suggesting a block in differentiation at the pro-B cell stage. The B220(-) phenotype was retained in one of the cell lines while the other was B220(+). When the two cell lines were transplanted into syngeneic mice, all animals developed the same B-lymphoblastic leukemia within 2-weeks. Thus, the murine model described here closely mimics the human disease with bilineage myeloid and B-cell leukemia/lymphoma which provides a representative model to investigate therapeutic intervention and a better understanding of the etiology of the disease.
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PMID:Acute progression of BCR-FGFR1 induced murine B-lympho/myeloproliferative disorder suggests involvement of lineages at the pro-B cell stage. 2270 16

B-lymphoblastic leukemia (B-ALL) is a neoplasm of precursors committed to B-cell lineage, whereas myeloproliferative neoplasm (MPN) is a clonal proliferation derived from myeloid stem cells. Concurrent B-ALL with MPN is uncommon except in the presence of abnormalities of the PDGFRA, PDGFRB, or FGFR1 genes or the BCR-ABL1 fusion gene. Herein, we describe a rare concurrence, B-ALL with MPN without the aforementioned genetic aberrations, in a 64-year-old male patient. The patient was initially diagnosed with B-ALL with normal karyotype and responded well to aggressive chemotherapy but had sustained leukocytosis and splenomegaly. The posttreatment restaging bone marrow was free of B-ALL but remained hypercellular with myeloid predominance. Using a single nucleotide polymorphism microarray study, we identified a copy neutral loss of heterozygosity at the terminus of 1p in the bone marrow samples taken at diagnosis and again at remission, 49% and 100%, respectively. Several additional genetic abnormalities were present in the initial marrow sample but not in the remission marrow samples. Retrospective molecular studies detected a MPL W515S homozygous mutation in both the initial and remission marrows for B-ALL, at 30-40% and 80% dosage effect, respectively. In summary, we present a case of concurrent B-ALL and MPN and demonstrate a stepwise cytogenetic and molecular approach to the final diagnosis.
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PMID:Concurrence of B-lymphoblastic leukemia and myeloproliferative neoplasm with copy neutral loss of heterozygosity at chromosome 1p harboring a MPL W515S mutation. 2545 99

Although the Janus kinase (JAK) inhibitor ruxolitinib has long been the only drug licensed for treatment of the classic Philadelphia chromosome negative (Ph-) myeloproliferative neoplasms, years of drug development efforts have begun to bear fruit with the recent approval of a novel monopegylated interferon alfa-2b, ropeginterferon alfa, for patients with polycythemia vera without symptomatic splenomegaly in Europe. Several newer JAK inhibitors (fedratinib, pacritinib, momelotinib) have shown activity in phase 3 trials in patients with myelofibrosis but have, for various reasons, not yet received regulatory approval; all these agents, however, remain in active clinical development. Many other agents with diverse mechanisms of action are being explored in clinical trials in patients with myelofibrosis, both as single agents and in combination with ruxolitinib. Besides splenomegaly and symptoms, improvement of anemia has become a new focus of drug development in myelofibrosis. Ruxolitinib appears promising also in chronic neutrophilic leukemia, where mutations in CSF3R are common. Pemigatinib, a potent and selective inhibitor of fibroblast growth factor receptor (FGFR), has shown impressive efficacy in a small registration-directed trial in patients with FGFR1-rearranged myeloid/lymphoid neoplasms. Finally, avapritinib, a highly potent and selective inhibitor of KITD816V, has demonstrated unprecedented response rates in patients with advanced systemic mastocytosis.
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PMID:Novel treatment strategies for myeloproliferative neoplasms. 3159 41