Treatment outcomes for patients with myelodysplastic syndrome/myeloproliferative neoplasms with ring sideroblasts and thrombocytosis

2021 ◽  
pp. 1-6
Author(s):  
Rami Komrokji ◽  
Megan Melody ◽  
Najla al Ali ◽  
Onyee Chan ◽  
Virginia Klimek ◽  
...  
2010 ◽  
Vol 103 (8) ◽  
pp. 823-827 ◽  
Author(s):  
Khalil M. Charafeddine ◽  
Georges Y. Ibrahim ◽  
Rami A. Mahfouz ◽  
Ghazi S. Zaatari ◽  
Ziad M. Salem

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 264-272 ◽  
Author(s):  
Mario Cazzola ◽  
Luca Malcovati ◽  
Rosangela Invernizzi

Abstract According to the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues, myelodysplastic/myeloproliferative neoplasms are clonal myeloid neoplasms that have some clinical, laboratory, or morphologic findings that support a diagnosis of myelodysplastic syndrome, and other findings that are more consistent with myeloproliferative neoplasms. These disorders include chronic myelomonocytic leukemia, atypical chronic myeloid leukemia (BCR-ABL1 negative), juvenile myelomonocytic leukemia, and myelodysplastic/myeloproliferative neoplasms, unclassifiable. The best characterized of these latter unclassifiable conditions is the provisional entity defined as refractory anemia with ring sideroblasts associated with marked thrombocytosis. This article focuses on myelodysplastic/myeloproliferative neoplasms of adulthood, with particular emphasis on chronic myelomonocytic leukemia and refractory anemia with ring sideroblasts associated with marked thrombocytosis. Recent studies have partly clarified the molecular basis of these disorders, laying the groundwork for the development of molecular diagnostic and prognostic tools. It is hoped that these advances will soon translate into improved therapeutic approaches.


Blood ◽  
2018 ◽  
Vol 132 (23) ◽  
pp. 2470-2483 ◽  
Author(s):  
Shiro Tara ◽  
Yusuke Isshiki ◽  
Yaeko Nakajima-Takagi ◽  
Motohiko Oshima ◽  
Kazumasa Aoyama ◽  
...  

Abstract BCOR, encoding BCL-6 corepressor (BCOR), is X-linked and targeted by somatic mutations in various hematological malignancies including myelodysplastic syndrome (MDS). We previously reported that mice lacking Bcor exon 4 (BcorΔE4/y) in the hematopoietic compartment developed NOTCH-dependent acute T-cell lymphoblastic leukemia (T-ALL). Here, we analyzed mice lacking Bcor exons 9 and 10 (BcorΔE9-10/y), which express a carboxyl-terminal truncated BCOR that fails to interact with core effector components of polycomb repressive complex 1.1. BcorΔE9-10/y mice developed lethal T-ALL in a similar manner to BcorΔE4/y mice, whereas BcorΔE9-10/y hematopoietic cells showed a growth advantage in the myeloid compartment that was further enhanced by the concurrent deletion of Tet2. Tet2Δ/ΔBcorΔE9-10/y mice developed lethal MDS with progressive anemia and leukocytopenia, inefficient hematopoiesis, and the morphological dysplasia of blood cells. Tet2Δ/ΔBcorΔE9-10/y MDS cells reproduced MDS or evolved into lethal MDS/myeloproliferative neoplasms in secondary recipients. Transcriptional profiling revealed the derepression of myeloid regulator genes of the Cebp family and Hoxa cluster genes in BcorΔE9-10/y progenitor cells and the activation of p53 target genes specifically in MDS erythroblasts where massive apoptosis occurred. Our results reveal a tumor suppressor function of BCOR in myeloid malignancies and highlight the impact of Bcor insufficiency on the initiation and progression of MDS.


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