Cytogenomic characterization of double minute heterogeneity in therapy related acute myeloid leukemia

Research output: Contribution to journalArticle

Abstract

Breast 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. Genetic abnormalities in the leukemia cells included amplification of MYC and KMT2A as double minutes, and deletion and mutational inactivation of TP53 Concurrent amplification of different genes at different levels and on different double minutes, we have named “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.

Original languageEnglish (US)
Pages (from-to)69-75
Number of pages7
JournalCancer Genetics
Volume238
DOIs
StatePublished - Oct 1 2019

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Acute Myeloid Leukemia
Gene Amplification
docetaxel
Leukemia
Breast Neoplasms
Chromosomes, Human, Pair 8
Neoplasms
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 17
Alkylating Agents
Anthracyclines
Carboplatin
Myelodysplastic Syndromes
Adjuvant Chemotherapy
Microarray Analysis
Karyotype
Therapeutics
Radiation
Genes

Keywords

  • Amplification
  • Breast cancer
  • Double minutes
  • KMT2A
  • MYC
  • Secondary AML

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

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title = "Cytogenomic characterization of double minute heterogeneity in therapy related acute myeloid leukemia",
abstract = "Breast 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. Genetic abnormalities in the leukemia cells included amplification of MYC and KMT2A as double minutes, and deletion and mutational inactivation of TP53 Concurrent amplification of different genes at different levels and on different double minutes, we have named “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.",
keywords = "Amplification, Breast cancer, Double minutes, KMT2A, MYC, Secondary AML",
author = "Prasad Koduru and Weina Chen and Barbara Haley and Kevin Ho and Dwight Oliver and Kathleen Wilson",
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AU - Koduru, Prasad

AU - Chen, Weina

AU - Haley, Barbara

AU - Ho, Kevin

AU - Oliver, Dwight

AU - Wilson, Kathleen

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Breast 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. Genetic abnormalities in the leukemia cells included amplification of MYC and KMT2A as double minutes, and deletion and mutational inactivation of TP53 Concurrent amplification of different genes at different levels and on different double minutes, we have named “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.

AB - Breast 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. Genetic abnormalities in the leukemia cells included amplification of MYC and KMT2A as double minutes, and deletion and mutational inactivation of TP53 Concurrent amplification of different genes at different levels and on different double minutes, we have named “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.

KW - Amplification

KW - Breast cancer

KW - Double minutes

KW - KMT2A

KW - MYC

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