Cytogenomic Characterization of Double Minute Heterogeneity in Therapy Related Acute Myeloid Leukemia

Publication date: Available online 6 August 2019Source: Cancer GeneticsAuthor(s): Prasad Koduru, Weina Chen, Barbara Haley, Kevin Ho, Dwight Oliver, Kathleen WilsonAbstractBreast cancer patients treated with adjuvant chemotherapy regimens containing alkylating agents and anthracyclines are at an increased risk for secondary myeloid malignancies, either acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Complex genomic changes (karyotypes and/or gene amplification) accompany the development of the secondary neoplasms. Here we present a unique case of a breast cancer patient who developed secondary AML within 18 months of treatment with trastuzumab, pertuzumab, docetaxel, carboplatin (TCHP) and radiation. Leukemia cells had catastrophic alterations in chromosomes 8, 11, and 17. Concurrent genetic abnormalities in the leukemia cells included amplification of MYC and KMT2A, and deletion and mutational inactivation of TP53. MYC and KMT2A amplified at different levels and on different double minutes, which we called as double minute heterogeneity. Clinically, this case highlights the need to identify genes amplified in secondary myeloid malignancies by cytogenomic microarray (CMA) analysis since these may have therapeutic implications.
Source: Cancer Genetics - Category: Cancer & Oncology Source Type: research

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This study proposed a pilot study of a new tool for a reliable and accurate stratification of patients with acute leukemia based on an integrative model of leukemia behavior, cell characterization, and clinical features, in addition, to an evaluation of intra-tumor and inter-tumor heterogeneity. Together our approach allows us to introduce an integrative quantitative approach to use zebrafish and tumor characterization as a prediction tool for the behavior of acute leukemia in young adults. Materials and Methods Animal Care and Handling Zebrafish wild-type (A/B and TAB5) adults were raised and maintained according to st...
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research
CONCLUSION: Presence of multiple TP53 abnormalities can be observed in up to 13% of patients with MDS or AML. The number of TP53 abnormalities does not seem to affect the survival of patients with MDS, but is associated with worse OS in AML. In addition, although GOF mutations do not seem to affect outcome of pts with MDS, these mutations were associated with worse OS than LOF in pts with AML. Clonal size of TP53 mutations as well as their clearance in therapy correlate with survival outcomes.FigureDisclosuresSasaki: Otsuka Pharmaceutical: Honoraria. Kadia: Jazz: Consultancy, Research Funding; Jazz: Consultancy, Research F...
Source: Blood - Category: Hematology Authors: Tags: 617. Acute Myeloid Leukemia: Biology, Cytogenetics, and Molecular Markers in Diagnosis and Prognosis: Poster II 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
CONCLUSION Cognitive impairment can affect daily functioning, quality of life, and capacity to work in patients with cancer and those in remission. Consequently, cognitive assessment is now an important and necessary part of a comprehensive oncological care plan. Cancer-related cognitive impairment might be due to the direct effects of the cancer itself, nonspecific factors, or comorbid conditions that are independent of the disease and/or due to the adverse effects of the treatment or combination of treatments given for the disease. The prevalence and extent of cognitive impairment associated with cancer is recognized but...
Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Cognition Current Issue Neuro oncology Neurology Review cancer chemotherapy cognitive impairment neuropsychological assessment treatment Source Type: research
CONCLUSIONSAdjuvant chemotherapy is associated with a small but significant increase in the risk of AML and MDS, especially with regimens that include A. Longer follow‐up is needed to confirm that risk is not increased with the recently adopted TC regimen. Cancer 2017. © 2017 American Cancer Society.
Source: Cancer - Category: Cancer & Oncology Authors: Tags: Original Article Source Type: research
We examined acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) events among 9679 women treated for breast cancer on four adjuvant Alliance for Clinical Trials in Oncology trials with>90  months of follow-up in order to better characterize the risk for AML/MDS in older patients receiving anthracyclines.MethodsWe used multivariable Cox regression to examine factors associated with AML/MDS, adjusting for age ( ≥65 vs.
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
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...
Source: Oncotarget - Category: Cancer & Oncology Tags: Oncotarget Source Type: research
The therapy related myeloid neoplasms (t-MN) include the cases of therapy related myelodysplastic syndrome (t-MDS) and therapy related acute myeloid leukemia (t-AML) that occurs as a late complication of chemotherapy and/or radiotherapy administered to treat a previous neoplastic disease [1]. The alkylating agents and the topoisomerase II inhibitors are commonly implicated in the etiology of the disease, with a shorter latency period, 1 –5 years, for the topoisomerase II inhibitors. Most of patients with t-AML/t-MDS show an abnormal karyotype.
Source: Leukemia Research - Category: Hematology Authors: Tags: Editorial Source Type: research
Abstract Risk of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) post-breast cancer treatment with adjuvant chemotherapy and granulocyte colony-stimulating factors (G-CSF) is not fully characterized. Our objective was to estimate MDS/AML risk associated with specific breast cancer treatments. We conducted a retrospective cohort study of women aged ≥66 years with stage I–III breast cancer between 2001 and 2009 using the Surveillance, Epidemiology, and End Results-Medicare database. Women were classified as receiving treatment with radiation, chemotherapy, and/or G-CSF. We used multivar...
Source: Breast Cancer Research and Treatment - Category: Cancer & Oncology Source Type: research
Conclusion In this large early-stage breast cancer cohort, MN risk after radiation and/or adjuvant chemotherapy was low but higher than previously described. Risk continued to increase beyond 5 years. Individual risk of MN must be balanced against the absolute survival benefit of adjuvant chemotherapy.
Source: Journal of Clinical Oncology - Category: Cancer & Oncology Authors: Tags: Radiation, Chemotherapy, Combined Modality Breast Cancer Source Type: research
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