Leukemia research
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Some patients receiving a tyrosine kinase inhibitor (TKI) for the first-line treatment of chronic phase chronic myeloid leukemia (CML-CP) experience intolerable adverse events. Management strategies include dose adjustments, interrupting or discontinuing therapy, or switching to an alternative TKI. ⋯ Nilotinib 300 mg bid shows minimal cross intolerance in patients with CML-CP who have prior toxicities to other TKIs and can lead to deep molecular responses.
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Randomized Controlled Trial
The impact of oral arsenic and all-trans-retinoic acid on coagulopathy in acute promyelocytic leukemia.
The aim of our study was to evaluate the impact of oral arsenic (the realgar-indigo naturalis formula, RIF) and all-trans retinoic acid (ATRA) on coagulopathy in acute promyelocytic leukemia (APL) compared with intravenous arsenic trioxide (ATO) and ATRA during induction. Mitoxantrone was added to all the patients at a dose of 1.4mg/m2 per day for 5-7 days. D-dimer levels, prothrombin time (PT), fibrinogen (Fbg) levels and the platelet count were comparably analyzed among 83 newly diagnosed APL patients treated with RIF (n=45) or with ATO (n=38). ⋯ In the 17 patients with a DIC score <4, prompt recovery of Fbg levels (P=0.028) was observed in the RIF group compared with that in the ATO group (P=0.401). RIF and ATO showed similar effects on the recovery of coagulopathy in APL patients. RIF had a potential beneficial effect in accelerating the recovery of thrombocytopenia and hypofibrinogenemia for subclinical DIC patients.
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As the main component of traditional Chinese medicine realgar, arsenic disulfide (As2S2) is widely used in treating myelodysplastic syndromes (MDS). The goal of the current study is to assess the effects of As2S2 on bone marrow mononuclear cells (BMMNC) of MDS. ⋯ As2S2 could inhibit cell proliferation and induce apoptosis through histone acetylation modulation in MDS. Similar to SAHA, As2S2 could reduce TLR2 activation and increase GATA-1 expression. Current data suggest epigenetic and immunological alternations are involved in therapeutic mechanisms of realgar in the treatment of MDS.
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Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. ⋯ Further fluorescence in situ hybridization (FISH) showed cryptic insertion of ABL into BCR gene on chromosome 22, and DNA sequencing with alternative primer sets demonstrated the presence of an e13a3 BCR-ABL1 fusion. She was diagnosed as CML and received imatinib 400 mg/day. A follow-up BCR-ABL1 FISH analysis demonstrated a markedly reduced BCR-ABL1 fusion rate of 0 after 6months treatment, indicating a complete cytogenetic response.
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NPM1 insertion mutations represent a common recurrent genetic abnormality in acute myeloid leukemia (AML) patients. The frequency of these mutations varies from approximately 30% overall up to 50% in patients with a normal karyotype. Several recent studies have exploited advances in massively parallel sequencing technology to shed light on the complex genomic landscape of AML. ⋯ Mutations associated with cell signaling pathways (FLT3, NRAS, and PTPN11) are also frequently encountered in NPM1-mutated AML cases, but had relatively low VAFs (7.0-11.9%). No cases of NPM1-mutated AML with a concurrent IDH2R172 mutation were observed, suggesting that these variants are mutually exclusive. Overall, these data suggest that NPM1 mutations are a secondary or late event in the pathogenesis of AML and are preceded by founder mutations in genes that may be associated with recently described preclinical states such as clonal hematopoiesis of indeterminate potential or clonal cytopenias of undetermined significance.