A novel NUP98/RARG gene fusion in acute myeloid leukemia resembling acute promyelocytic leukemia.

Chromosomal translocations in hematological malignancies often result in novel fusion chimeric genes. We report a case of acute myeloid leukemia with a clonal translocation t(11;12)(p15;q13) displaying morphologic and immunophenotypic features resembling the classical hypergranular subtype of acute promyelocytic leukemia. The gene fused to NUP98 (nucleoporin 98) was detected by comparative genomic hybridization array as the retinoid acid receptor gamma gene (RARG). The involvement of RARG in a chimeric fusion transcript has not been reported previously in human leukemia.

Clinical features and course of refractory anemia with ring sideroblasts associated with marked thrombocytosis.

BACKGROUND: Refractory anemia with ring sideroblasts associated with marked thrombocytosis was proposed as a provisional entity in the 2001 World Health Organization classification of myeloid neoplasms and also in the 2008 version, but its existence as a single entity is contested. We wish to define the clinical features of this rare myelodysplastic/myeloproliferative neoplasm and to compare its clinical outcome with that of refractory anemia with ring sideroblasts and essential thrombocythemia. DESIGN AND METHODS: We conducted a collaborative retrospective study across Europe. Our database included 200 patients diagnosed with refractory anemia with ring sideroblasts and marked thrombocytosis. For each of these patients, each patient diagnosed with refractory anemia with ring sideroblasts was matched for age and sex. At the same time, a cohort of 454 patients with essential thrombocythemia was used to compare outcomes of the two diseases. RESULTS: In patients with refractory anemia with ring sideroblasts and marked thrombocytosis, depending on the Janus Kinase 2 V617F mutational status (positive or negative) or platelet threshold (over or below 600 × 10(9)/L), no difference in survival was noted. However, these patients had shorter overall survival and leukemia-free survival with a lower risk of thrombotic complications than did patients with essential thrombocythemia (P<0.001) but better survival (P<0.001) and a higher risk of thrombosis (P=0.039) than patients with refractory anemia with ring sideroblasts. CONCLUSIONS: The clinical course of refractory anemia with ring sideroblasts and marked thrombocytosis is better than that of refractory anemia with ring sideroblasts and worse than that of essential thrombocythemia. The higher risk of thrombotic events in this disorder suggests that anti-platelet therapy might be considered in this subset of patients. From a clinical point of view, it appears to be important to consider refractory anemia with ring sideroblasts and marked thrombocytosis as a distinct entity.

Tumor lysis syndrome in patients with acute myeloid leukemia: identification of risk factors and development of a predictive model.

BACKGROUND: Despite the prophylactic use of allopurinol, tumor lysis syndrome (TLS)-related morbidity and mortality still occur in a number of patients with acute myeloid leukemia (AML). The aim of this study was: (i) to analyze the incidence and outcome of TLS in a large series of patients with AML receiving hyperhydration and allopurinol, (ii) to identify risk factors for TLS, and (iii) to develop a prognostic scoring system for estimating individual risk of TLS. DESIGN AND METHODS: The study included 772 adult patients with AML receiving induction chemotherapy between 1980 and 2002. TLS was divided into laboratory TLS (LTLS) or clinical TLS (CTLS). The population study was randomly divided into training and test subsets, so that a prognostic model for CTLS was developed in one set and validated in the other. RESULTS: Overall, 130 patients (17%) developed TLS (5% CTLS and 12% LTLS). Unlike LTLS, CTLS was associated with a higher rate of death from induction therapy. Multivariate analysis showed that pretreatment serum lactate dehydrogenase (LDH) levels above laboratory normal values, creatinine >1.4 mg/dL, uric acid >7.5 mg/dL and white blood cell (WBC) counts >25 x 10(9)/L were independent risk factors for CTLS and LTLS. The scoring system, based on pretreatment WBC counts, and uric acid and LDH serum levels, had excellent discrimination and was accurate for predicting CTLS and LTLS. CONCLUSIONS: TLS is frequently observed in AML patients during induction therapy. Only the development of CTLS had an impact on higher mortality rate from induction therapy. The scoring system derived from this study can be used to obtain an accurate estimate of the individual risk of TLS, allowing for risk-adapted prophylaxis against this complication.

Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): Clinical and biological features and comparison with other acute myeloid leukemias with cytogenetic aberrations involving long arm of chromosome 3.

OBJECTIVES: To compare, from a biological and clinical perspective, a significant group of patients with AML with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) with another group of AML carrying different abnormalities of 3q at q21 or q26, the latter named as the AML abn(3q) group. METHODS: We developed a national survey with the participation of 13 Spanish hospitals, and retrospectively reviewed (from 1990 to 2010) these subtypes of AML. Fifty-five patients were collected: 35 with AML inv(3)/t(3;3) and 20 with AML abn(3q). A data collecting page that included main features at diagnosis, therapeutic approach and response, and survival variables, was distributed and completed. RESULTS: We did not find significant differences in sex, age, history of myelodysplastic syndrome or chemo-/radiotherapy, clinical presentation, WBC and platelet counts, hemoglobin level, blasts immunophenotype, serum lactatedehydrogenase, peripheral blood and bone marrow cellular dysplasia, and bone marrow biopsy findings. Although the association with monosomy 7 was significantly more frequent in AML inv(3)/t(3;3), this did not seem to influence outcome. The lack of response to the different modalities of treatment and the aggressive course of the disease were the standard in both cohorts of patients. DISCUSSION: Although not yet recognized by the World Health Organization classification, our results are in agreement with the findings of other authors, who include both subsets of AML together in the same group of adverse prognosis. CONCLUSION: In an attempt to simplify and bound entities with similar genetic background and clinical behavior, it would be desirable to bring together both subgroups of AML in a single section.