Hematopoietic malignancies account for 6% to 8% of new cancers diagnosed annually. In the year 2010, an estimated 43,050 new cases of leukemia were diagnosed, and 21,840 deaths were attributable to leukemias of all types. More »
Romiplostim, a synthetic protein that binds to and stimulates the thrombopoietin receptor, induced a rapid platelet response in adult patients with primary immune thrombocytopenia (ITP) and maintained a consistent safety profile in an international phase III trial. More »
Two recent reports show that the prognosis of MDS patients after secondary failure of hypomethylating drugs is poor, and switching from one failing hypomethylating drug to another cannot induce clinically significant responses. More »
Hematopoietic cell transplantation (HCT) is the IV infusion of hematopoietic stem and progenitor cells designed to establish marrow and immune function in patients with a variety of acquired and inherited malignant and nonmalignant disorders. More »
According to the fourth edition of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, the group of B-cell marginal zone lymphomas (MZL) comprises three different entities. More »
Myelodysplastic syndromes (MDS) are a group of hematologic malignancies of the pluripotent hematopoietic stem cells. These disorders are characterized by ineffective hematopoiesis, including abnormalities in proliferation, differentiation, and apoptosis. More »
Recently, we showed that increased miR-181a expression was associated with improved outcomes in cytogenetically normal acute myeloid leukemia (CN-AML). Interestingly, miR-181a expression was increased in CN-AML patients harboring CEBPA mutations, which are usually biallelic and associate with better prognosis. CEBPA encodes the C/EBP transcription factor. We demonstrate here that the presence of N-terminal CEBPA mutations and miR-181a expression are linked. Indeed, the truncated C/EBP-p30 isoform, which is produced from the N-terminal mutant CEBPA gene or from the differential translation of wild-type CEBPA mRNA and is commonly believed to have no transactivation activity, binds to the miR-181a-1 promoter and up-regulates the microRNA expression. Furthermore, we show that lenalidomide, a drug approved for myelodysplasticsyndromes and multiple myeloma, enhances translation of the C/EBP-p30 isoform, resulting in higher miR-181a levels. In xenograft mouse models, ectopic miR-181a
23061809 2012 12 17 2013 02 06 1600-0609 90 1 Jan Eur. J. Haematol. 79-80 10.1111/ejh.12024 Matsuda Akira A Germing Ulrich U Miyazaki Yasushi Y eng Letter 2012 11 22 England Eur J Haematol 8703985 0902-4441 IM pathology classification diagnosis.
Treatment of relapse after allogenic stem cell transplantation (allo-SCT) is challenging. The efficacy of donor leukocyte infusions (DLI) is excellent in chronic phase chronic myeloid leukaemia but limited in other disorders. We present a patient who relapsed 10 months after reduced intensity conditioning allo-SCT for a myelodysplastic/ myeloproliferative neoplasm with myelofibrosis despite receiving escalating doses of DLI for incomplete chimerism. He finally achieved complete remission with full whole blood and T-cell donor chimerism after DLI preceded by lymphodepletion chemotherapy. This case demonstrates that chemotherapy prior to DLI is a useful approach for treating relapses of relatively slowly progressive diseases, such as myeloproliferative diseases or myelodysplasticsyndromes.
23258901 2012 12 21 2013 02 15 1528-0020 120 26 Dec 20 Blood 5247-9 10.1182/blood-2012-09-457945 Churpek Jane E JE Nickels Eric E Marquez Rafael R Rojek Katarzyna K Liu Bohao B Lorenz Rachelle R Lepore Janet J Madzo Jozef J Wickrema Amittha A Artz
Myelodysplasticsyndromes (MDS) are malignant clonal disorders of haematopoietic stem cells and their microenvironment, affecting older individuals (median age 70 years). Unique features that are associated with MDS - but which are not necessarily present in every patient with MDS - include excessive apoptosis in maturing clonal cells, a pro-inflammatory bone marrow microenvironment, specific chromosomal abnormalities, abnormal ribosomal protein biogenesis, the presence of uniparental disomy, and mutations affecting genes involved in proliferation, methylation and epigenetic modifications. Although emerging insights establish an association between molecular abnormalities and the phenotypic heterogeneity of MDS, their origin and progression remain enigmatic.