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Molecular analysis of myelodysplastic syndrome with isolated del(5q) reveals a specific spectrum of molecular mutations with prognostic impact: a study on 123 patients and 27 genes.
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Molecular analysis of myelodysplastic syndrome with isolated del(5q) reveals a specific spectrum of molecular mutations with prognostic impact: a study on 123 patients and 27 genes.

Haematologica. 2017 Jun 22;:

Authors: Meggendorfer M, Haferlach C, Kern W, Haferlach T

Abstract
The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, giving with morphological features the diagnosis of myelodysplastic syndrome with isolated del(5q). These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia. However, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated del(5q) diagnosed following the World Health Organization classifications 2008 and 2016 by sequencing 27 genes. A great proportion of patients showed no or only one mutation. Only seven genes showed mutation frequencies >5% (SF3B1, DNMT3A, TP53, TET2, CSNK1A1, ASXL1, JAK2). However, the pattern of recurrently mutated genes was comparable to other myelodysplastic syndrome subtypes by comparison to a reference cohort, except of TP53 that was significantly more often mutated in myelodysplastic syndrome with isolated del(5q). As expected, SF3B1 was frequently mutated and correlated with ring sideroblasts, while JAK2 mutations correlated with elevated platelet counts. Surprisingly, SF3B1 mutations led to significantly worse prognosis within cases with isolated del(5q), but showed a comparable outcome to other myelodysplastic syndrome subtypes with SF3B1 mutation. However, addressing genetic stability in follow-up cases might suggest different genetic mechanisms for progression to secondary acute myeloid leukemia compared to overall myelodysplastic syndrome patients.

PMID: 28642303 [PubMed - as supplied by publisher]




Residual erythropoiesis protects against myocardial hemosiderosis in transfusion-dependent thalassemia by lowering labile plasma iron via transient generation of apotransferrin.
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Residual erythropoiesis protects against myocardial hemosiderosis in transfusion-dependent thalassemia by lowering labile plasma iron via transient generation of apotransferrin.

Haematologica. 2017 Jun 22;:

Authors: Garbowski MW, Evans P, Vlachodimitropoulou E, Hider R, Porter JB

Abstract
Cardiosiderosis is a leading cause of mortality in transfusion-dependent thalassemias. Plasma non-transferrin-bound iron and its redox-active component, labile plasma iron, are key sources of iron loading in cardiosiderosis. Risk factors were identified in 73 patients with or without cardiosiderosis. Soluble transferrin receptor-1 levels were significantly lower in patients with cardiosiderosis (odds ratio 21). This risk increased when transfusion-iron loading rates exceeded the erythroid transferrin uptake rate (derived from soluble transferrin receptor-1) by >0.21mg/kg/d (odds ratio 48). Labile plasma iron was >3-fold higher where this uptake rate threshold was exceeded, but non-transferrin-bound iron and transferrin saturation were comparable. Cardiosiderosis risk was also decreased in patients with low liver iron, ferritin and labile plasma iron, or high bilirubin, reticulocyte counts or hepcidin. We hypothesized that high erythroid transferrin uptake rate decreases cardiosiderosis through increased erythroid re-generation of apotransferrin. To test this, iron uptake and intracellular reactive oxygen species were examined in HL-1 cardiomyocytes under conditions modelling transferrin effects on non-transferrin-bound iron speciation with ferric citrate. Intracellular iron and reactive oxygen species increased with ferric citrate concentrations especially where iron-to-citrate ratios exceeded 1:100, i.e. conditions favoring kinetically labile monoferric rather than oligomer species. Excess iron-binding equivalents of apotransferrin inhibited iron uptake, decreased intracellular reactive oxygen species and labile plasma iron, under conditions favoring monoferric species. In conclusion, high transferrin iron utilisation, relative to the transfusion-iron load rate, decreases the cardiosiderotic risk. A putative mechanism is the transient re-generation of apotransferrin by an active erythron, rapidly binding labile plasma iron-detectable ferric monocitrate species.

PMID: 28642302 [PubMed - as supplied by publisher]




The specific BTK inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B-cells with CD20 antibodies.
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The specific BTK inhibitor acalabrutinib (ACP-196) shows favorable in vitro activity against chronic lymphocytic leukemia B-cells with CD20 antibodies.

Haematologica. 2017 Jun 22;:

Authors: Golay J, Ubiali G, Introna M

PMID: 28642301 [PubMed - as supplied by publisher]




Center-level variation in accuracy of adverse event reporting in a clinical trial for pediatric acute myeloid leukemia: A report from the Children's Oncology Group.
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Center-level variation in accuracy of adverse event reporting in a clinical trial for pediatric acute myeloid leukemia: A report from the Children's Oncology Group.

Haematologica. 2017 Jun 22;:

Authors: Miller TP, Li Y, Kavcic M, Getz KD, Huang YV, Sung L, Alonzo TA, Gerbing R, Daves MH, Horton TM, Pulsipher MA, Pollard J, Bagatell R, Seif AE, Fisher BT, Luger S, Gamis AS, Adamson PC, Aplenc R

PMID: 28642300 [PubMed - as supplied by publisher]