Mutation analysis of therapy-related myeloid neoplasms

Publication date: April 2018 Source:Cancer Genetics, Volumes 222–223 Author(s): Takahiro Nishiyama, Yuichi Ishikawa, Naomi Kawashima, Akimi Akashi, Yoshiya Adachi, Hikaru Hattori, Yoko Ushijima, Hitoshi Kiyoi We analyzed the genetic mutation status of 13 patients with therapy-related myeloid neoplasms (t-MN). Consistent with previous reports, t-MN cells preferentially acquired mutations in TP53 and epigenetic modifying genes, instead of mutations in tyrosine kinase and spliceosome genes. Furthermore, we compared the mutation status of three t-MN cells with each of the initial lymphoid malignant cells, and identified common mutations among t-MN and the initial malignant cells in two patients. In a patient who developed chronic myelomonocytic leukemia (CMML) after follicular lymphoma (FL), TET2 mutation was identified in both CMML and FL cells. Notably, the TET2 mutation was also identified in peripheral blood cells in the disease-free period with the same allelic frequency as CMML and FL cells, but not in a germ-line control, indicating that the TET2 mutation occurred somatically in the initiating clone for both malignant cells. On the other hand, a germ-line MYB mutation was identified in a patient who developed myelodysplastic syndromes (MDS) after FL. These results suggest that germ-line deposition and clonal hematopoiesis are closely associated with t-MN susceptibility; however, further analysis is necessary to clarify the mechanism required to provide the initiatin...
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research

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This study analyzes patient and hospital characteristics of patients undergoing BMT, in addition the study describes resource utilization and outcomes of BMT among various hematological cancers.Methods: We performed a retrospective cohort analysis of the National Inpatient Sample 2014 Database (HCUP-NIS). Patients were included in the study if they had a procedure diagnosis of BMT and a medical diagnosis of acute or chronic leukemia (ALL, AML, CLL, CML), lymphoma (HL and NHL), MM, MDS or HLH. HSCT or BMT includes both Allogeneic and Autologous Stem Cell Transplant however we did not differentiate one from the other since B...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Poster III Source Type: research
Background: Various pro-inflammatory and stress-related stimuli activate p38 mitogen-activated protein kinase (p38MAPK), triggering cascades of cell proliferation, differentiation, and apoptosis signaling. We have previously found that inflammatory cytokines promote growth and survival in primary cells from acute myeloid leukemia (AML) patients. The downstream mediator of inflammatory pathways is p38MAPK, and blocking this regulator with kinase inhibitors abrogates inflammation signaling in AML cells.Methods: We used a functional ex vivo screening assay to identify small-molecule targeted inhibitors and inhibitor combinati...
Source: Blood - Category: Hematology Authors: Tags: 616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Poster II Source Type: research
Conclusion: Both myeloid and lymphoid-derived primary leukemia cells show sensitivity to combined inhibition of BCL2 and BTK with the combination of venetoclax and ibrutinib, suggesting this drug pair may have broad therapeutic indications.DisclosuresTyner: Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Genentech: Research Funding; Gilead: Research Funding; Constellation: Research Funding; Janssen: Research Funding; AstraZeneca: Research Funding; Incyte: Research Funding; Array: Research Funding; Aptose: Research Funding. Danilov: TG Therapeutics: Consultan...
Source: Blood - Category: Hematology Authors: Tags: 802. Chemical Biology and Experimental Therapeutics: New Targeted Therapies and Drug Development Source Type: research
The first two authors and last two authors contributed equally.Genome-wide association studies (GWAS) have identified risk loci for Acute Lymphoblastic Leukemia (ALL), Chronic Lymphoblastic Leukemia (CLL) and Non-Hodgkin Lymphoma, however an Acute Myeloid Leukemia (AML) GWAS has not been published to date. We performed a GWAS to identify AML and Myelodysplastic Syndrome (MDS) risk loci using a nested case-control study design in the DISCOVeRY-BMT cohorts which includes almost 2000 AML and MDS patients as cases and 2813 unrelated donors as controls.Genotyping was performed using the Illumina Human OmniExpress BeadChip and i...
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster I Source Type: research
Objective: To investigate the clinical features of 2nd hematological malignancies post to the initial cancer treatment.METHODS: A retrospective study was performed to analyze the available clinical data of 116 patients diagnosed with 2nd hematologic malignancies after treatment of various malignant tumors from June 1998 to June 2018 at Sun Yat-sen University cancer center.RESULTS: The characteristics of the 116 patients diagnosed with 2nd hematological cancer post to initial cancer treatment were indicated as following: 62 males and 54 females. The primary tumor category was grouped as (according to ICD-10 International Di...
Source: Blood - Category: Hematology Authors: Tags: 904. Outcomes Research-Malignant Conditions Source Type: research
Conclusions: The proportion of Medicare beneficiaries with HM who die in inpatient setting (39%) or are admitted to ICU (39%) in the last month of life is higher than in a contemporary population of Medicare beneficiaries with cancer (22% and 27%, respectively, in 2009 per Teno et al., JAMA 2013). Across the spectrum of HM, which vary in prognosis and clinical course, use of hospice services is associated with markedly improved measures of EOL care quality, as well as lower Medicare spending in the last month of life. However, only 47% of beneficiaries with HM use hospice services (compared with 59% in Teno et al.). Chemot...
Source: Blood - Category: Hematology Authors: Tags: 902. Health Services Research-Malignant Diseases: Population Studies, End-of-life, and Palliative Care Source Type: research
Background: Immune reconstitution after allogeneic stem cell transplantation (SCT) is a complicated process influenced by factors such as preconditioning regimens, graft-versus-host disease (GVHD) prophylaxis, and grafts. We studied the association between the kinetics of lymphocyte subsets and transplant outcome to clarify the differences in immune reconstitution after hematopoietic cell transplantation according to stem cell sources and its clinical significance.Patients and Methods: Clinical data were collected from patients' medical charts at Kanagawa Cancer Center, Yokohama, Japan. Patients with hematological malignan...
Source: Blood - Category: Hematology Authors: Tags: 722. Clinical Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster I Source Type: research
Conclusions:We present the largest experience in EMH without associated MPN, in adults. We describe associated conditions and elaborate further on "idiopathic" EMH (n=12), which often represented an incidental discovery during evaluation of unrelated symptoms. None of the patients with idiopathic EMH harbored occult malignancies or subsequently developed MPN or other myeloid malignancies. Our observations do not support undertaking extensive investigations targeting MPN or other malignancies in idiopathic EMH and simple monitoring might be adequate.DisclosuresNo relevant conflicts of interest to declare.
Source: Blood - Category: Hematology Authors: Tags: 634. Myeloproliferative Syndromes: Clinical Source Type: research
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
Conclusions: Sepsis is associated with increased or decreased risks for a small group of cancers. Factors that may explain these associations include etiologic effects of bacterial infections, inflammation, or use of antibiotics. Other associations may reflect the presence of precursor conditions (e.g., cirrhosis, colorectal polyps) or patterns in ascertainment of cancer and screening. PMID: 29982318 [PubMed - as supplied by publisher]
Source: Clinical Prostate Cancer - Category: Cancer & Oncology Authors: Tags: Clin Infect Dis Source Type: research
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