Dna-hypomethylating agents as epigenetic therapy before and after allogeneic hematopoietic stem cell transplantation in myelodysplastic syndromes and juvenile myelomonocytic leukemia

Publication date: Available online 9 November 2017 Source:Seminars in Cancer Biology Author(s): Christian Flotho, Sebastian Sommer, Michael Lübbert Myelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular responsiveness to epigenetic therapy with the DNA-hypomethylating agents 5-azacytidine (azacitidine) or decitabine. However, hypomethylating therapy does not eradicate the malignant clone in MDS or JMML and allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment option. An emerging concept with intriguing potential is the combination of hypomethylating therapy and HSCT. Possible advantages include disease control with good tolerability during donor search and HSCT preparation, improved antitumoral alloimmunity, and reduced risk of relapse even with non-myeloablative regimens. Herein we review the current role of pre- and post-transplant therapy with hypomethylating agents in MDS and JMML.
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research

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Publication date: August 2018Source: The Lancet Haematology, Volume 5, Issue 8Author(s): Subhayan Chattopadhyay, Guoqiao Zheng, Amit Sud, Hongyao Yu, Kristina Sundquist, Jan Sundquist, Asta Försti, Akseli Hemminki, Richard Houlston, Kari HemminkiSummaryBackgroundAlthough advances in the treatment of myeloid neoplasms have led to improved patient survival, this improvement has been accompanied by an increased risk of second primary cancer (ie, the risk of another cancer after myeloid neoplasia). We aimed to assess bi-directional associations between myeloid cancers and other cancers—ie, development of second prim...
Source: The Lancet Haematology - Category: Hematology Source Type: research
Application of next-generation sequencing (NGS) panels is usually limited to diagnosis, prognosis, and development of personalized treatment strategies/targeted therapies for patients with myeloid malignancies e.g., Myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPN), and acute myelogenous leukemia (AML). Here we present a case of 3 year old male that presented with pancytopenia and splenomegaly. His initial bone marrow revealed mild to moderate fibrosis (normocellular; no increase in blasts).
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
Publication date: Available online 9 November 2017Source: Seminars in Cancer BiologyAuthor(s): Christian Flotho, Sebastian Sommer, Michael LübbertAbstractMyelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular resp...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
AbstractThe myelodysplastic syndromes, the chronic myeloproliferative neoplasms, and the acute myeloid leukemia are malignancies of the myeloid hematopoietic stem cells of the bone marrow. The diseases are characterized by a dysregulation of the immune system as both the cytokine milieu, immune phenotype, immune regulation, and expression of genes related to immune cell functions are deregulated. Several treatment strategies try to circumvent this deregulation, and several clinical and preclinical trials have shown promising results, albeit not in the same scale as chimeric antigen receptor T cells have had in the treatmen...
Source: Seminars in Immunopathology - Category: Pathology Source Type: research
Publication date: Available online 9 November 2017Source: Seminars in Cancer BiologyAuthor(s): Christian Flotho, Sebastian Sommer, Michael LübbertAbstractMyelodysplastic syndrome (MDS) is a clonal bone marrow disorder, typically of older adults, which is characterized by ineffective hematopoiesis, peripheral blood cytopenias and risk of progression to acute myeloid leukemia. Juvenile myelomonocytic leukemia (JMML) is an aggressive myeloproliferative neoplasm occurring in young children. The common denominator of these malignant myeloid disorders is the limited benefit of conventional chemotherapy and a particular resp...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Contributors : Hiroyoshi Kunimoto ; Cem Meydan ; Francine E Garrett-Bakelman ; Caroline Sheridan ; Tak Lee ; Yaseswini Neelamraju ; Ari Melnick ; Ross L LevineSeries Type : Methylation profiling by high throughput sequencingOrganism : Mus musculusRecent studies using next-generation sequencing technology have uncovered mutational landscapes of various myeloid malignancies (Cancer Genome Atlas Research Network, 2013; Yoshida et al., 2011). These genetic data revealed novel classes of mutations that commonly occur in patients with myeloid malignancies, including epigenetic regulators and spliceosomal genes. In addition, co-o...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Methylation profiling by high throughput sequencing Mus musculus Source Type: research
Contributors : Hiroyoshi Kunimoto ; Cem Meydan ; Francine E Garrett-Bakelman ; Caroline Sheridan ; Tak Lee ; Yaseswini Neelamraju ; Ari Melnick ; Ross L LevineSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusRecent studies using next-generation sequencing technology have uncovered mutational landscapes of various myeloid malignancies (Cancer Genome Atlas Research Network, 2013; Yoshida et al., 2011). These genetic data revealed novel classes of mutations that commonly occur in patients with myeloid malignancies, including epigenetic regulators and spliceosomal genes. In addition, co-oc...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research
Conclusion: The prevalence of PHD after PRRT with 177Lu-DOTATATE was 4% in our patient population. The median time at which PHD developed was 41 mo after the first PRRT cycle. The relative risk for developing a hematopoietic neoplasm was 2.7. No risk factors were found for the development of PHD in GEP NET patients.
Source: Journal of Nuclear Medicine - Category: Nuclear Medicine Authors: Tags: Clinical Source Type: research
Publication date: July 2017 Source:Clinical Lymphoma Myeloma and Leukemia, Volume 17, Supplement Author(s): Umang Patel, Rajyalakshmi Luthra, L. Jeffrey Medeiros, Keyur P. Patel The classification and risk stratification of myeloid neoplasms, including acute myeloid leukemia, myelodysplastic syndromes, myelodysplastic syndromes/myeloproliferative neoplasms, and myeloproliferative neoplasms, have increasingly been guided by molecular genetic abnormalities. Gene expression analysis and next-generation sequencing have led to the ever increasing discovery of somatic gene mutations in myeloid neoplasms. Mutations have been ide...
Source: Clinical Lymphoma Myeloma and Leukemia - Category: Cancer & Oncology Source Type: research
Gains and losses of chromosomes and specific chromosomal regions detected by conventional cytogenetic analysis are well-established markers of clinical significance in the majority of acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPNs). However, there are currently no set standards or practice guidelines describing incorporation of genome-wide testing for copy number aberrations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) by SNP-chromosomal microarrays (CMA) in the clinical evaluation of myeloid neoplasms.
Source: Cancer Genetics and Cytogenetics - Category: Genetics & Stem Cells Authors: Source Type: research
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