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.
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...
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.
Authors: Bertoli S, Sterin A, Tavitian S, Oberic L, Ysebaert L, Bouabdallah R, Vergez F, Sarry A, Bérard E, Huguet F, Laurent G, Prébet T, Vey N, Récher C Abstract Therapy-related acute myeloid leukemia (t-AML) is a heterogeneous entity most frequently related to breast cancer or lymphoproliferative diseases (LD). Population-based studies have reported an increased risk of t-AML after treatment of lymphomas. The aim of this study was to describe the characteristics and outcome of 80 consecutive cases of t-AML following treatment of LD. t-AML accounted for 2.3% of all AML cases, occurred 60 mont...
Myeloid disorders are a heterogeneous group of hematologic neoplasms that includes acute myeloid leukemia, myelodysplastic syndromes and myeloproliferative neoplasms. Cytogenetic testing has long served as a primary tool for risk stratification of myeloid disorders. However, a significant proportion of cases exhibit a normal karyotype and outcomes often vary among individuals with the same abnormal karyotype. Molecular genetic analysis in myeloid disorders has led to the discovery of recurrent somatic driver mutations, which allow for further risk stratification within cytogenetic groups as well as among the normal karyotype group.
For patients with myeloid malignancies (e.g. MDS, myeloproliferative neoplasms (MPN), and acute myelogenous leukemia (AML)), application of next-generation sequencing (NGS) panels is usually limited to diagnosis, prognosis, and development of personalized treatment strategies (i.e., targeted therapies). Here we present a case in which results from an NGS panel were used to determine sibling eligibility for hematopoietic stem cell transplant in a 17 year old male with MDS. Library preparation was performed with DNA extracted from the peripheral blood of both the patients, and an 11 year old female sibling, using Illumina's ...
CONCLUSION: The striking differences in the incidence patterns by histologic subtype strongly suggest a certain level of etiologic heterogeneity among hematological malignancies and support the pursuit of epidemiologic analysis by subtype for HMs in international studies. Age-standardized incidence rates are essential to analyze trends in risk, whereas the number of incident cases is necessary to make provisions for healthcare resources and to evaluate the overall burden of HM. PMID: 26973179 [PubMed - as supplied by publisher]
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CONCLUSION: This report updated the nationwide statistical analysis on myeloid malignancies since 2008, showing increasing incidence and improving trends in survival. PMID: 26770948 [PubMed]
Acute myeloid leukemia (AML) is an aggressive blood cancer that results from an abnormal expansion of uncontrollably proliferating myeloid progenitors that have lost the capacity to differentiate. AML encompasses many genetically distinct subtypes that predominantly develop de novo. However, AML can also arise from premalignant myeloid conditions, such as myelodysplastic syndrome (MDS) and myeloproliferative neoplasms (MPNs), or develop as the result of exposure to genotoxic agents used to treat unrelated malignancies.
Acute myeloid leukemia (AML) is an aggressive blood cancer that results from an abnormal expansion of uncontrollably proliferating myeloid progenitors that have lost the capacity to differentiate. AML encompasses many genetically distinct sub-types that predominantly develop de novo. However, AML can also arise from pre-malignant myeloid conditions, such as myelodysplastic syndrome (MDS), myeloproliferative neoplasms (MPNs) or develop as the result of exposure to genotoxic agents used to treat unrelated malignancies.