American Association for Cancer Research
00085472can161386-sup-166466_1_supp_3649396_5fcqwl.docx (53.59 kB)

Supplementary Materials from Mutational Landscape and Gene Expression Patterns in Adult Acute Myeloid Leukemias with Monosomy 7 as a Sole Abnormality

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journal contribution
posted on 2023-03-31, 00:28 authored by Ann-Kathrin Eisfeld, Jessica Kohlschmidt, Krzysztof Mrózek, Stefano Volinia, James S. Blachly, Deedra Nicolet, Christopher Oakes, Karl Kroll, Shelley Orwick, Andrew J. Carroll, Richard M. Stone, John C. Byrd, Albert de la Chapelle, Clara D. Bloomfield

Materials and Methods: Participating institutions. List of all institutions that participated in the study. Patients and treatments. Detailed information about patients included in the study and their treatments. Mutational profiling. Detailed information about the techniques used to perform the mutational profiling. Definition of clinical endpoints. Statistical definition of the used end point terms . Univariable outcome analysis. Listing of all parameters that were included in the univariable outcome analysis.



Coleman Leukemia Research Foundation

Pelotonia Fellowship Program

The Ohio Supercomputer Center



Monosomy of chromosome 7 is the most frequent autosomal monosomy in acute myeloid leukemia (AML), where it associates with poor clinical outcomes. However, molecular features associated with this sole monosomy subtype (-7 AML), which may give insights into the basis for its poor prognosis, have not been characterized. In this study, we analyzed 36 cases of -7 AML for mutations in 81 leukemia/cancer-associated genes using a customized targeted next-generation sequencing panel (Miseq). Global gene and miRNA expression profiles were also determined using paired RNA and small RNA sequencing data. Notably, gene mutations were detected in all the major AML-associated functional groups, which include activated signaling, chromatin remodeling, cohesin complex, methylation, NPM1, spliceosome, transcription factors, and tumor suppressors. Gene mutations in the chromatin remodeling groups were relatively more frequent in patients <60 years of age, who also had less mutations in the methylation and spliceosome groups compared with patients ≥60 years of age. Novel recurrent mutational events in AML were identified in the SMARCA2 gene. In patients ≥60 years of age, the presence of spliceosome mutations associated with a lower complete remission rate (P = 0.03). RNA sequencing revealed distinct gene and miRNA expression patterns between the sole -7 and non -7 AML cases, with reduced expression, as expected, of many genes and miRNAs mapped to chromosome 7, and overexpression of ID1, MECOM, and PTPRM, among others. Overall, our findings illuminate a number of molecular features of the underlying aggressive pathobiology in -7 AML patients. Cancer Res; 77(1); 207–18. ©2016 AACR.

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