Code - An integrative multiparametric approach stratifies distinct phenotypes of blast phase chronic myelomonocytic leukemia with differential maturation status and drug sensitivity profiles
Description
Approximately 30% of chronic myelomonocytic leukemia patients undergo transformation to a chemo-refractory blastic phase (BP-CMML). Seeking novel therapeutic approaches we profiled blast transcriptomes from 42 BP-CMMLs, observing extensive transcriptional heterogeneity and poor alignment to current AML classifications. BP-CMMLs displayed distinctive transcriptomic profiles, including enrichment for quiescence and variability in drug response signatures. Integrating clinical, immunophenotype and transcriptome parameters, RandomForest unsupervised clustering distinguished immature and mature subtypes characterized by differential expression of transcriptional modules, oncogenes, apoptotic regulators and patterns of surface marker expression. Subtypes differed in predicted response to AML drugs, validated ex vivo in primary samples. Iteratively refined stratification resolved a classification structure comprising five subtypes along a maturation spectrum, predictive of response to novel agents including consistent patterns for RTK, CDK, MTOR and MAPK inhibitors. Finally, we generated a clinically-applicable decision tree to stratify BP-CMML with high specificity and sensitivity, and potentially guide personalized drug selection for improved outcomes. ################### # Code description: # ################### Codes included within this data repository are to be used for figure reproduction or further exploration.
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Steps to reproduce
1) Clone/Download the code from the GitHub repository linked below or from the current Mendeley Data repository. 2) Download the input data in the Data.zip file from the Mendeley Data repository linked below and decompress on the same folder containing the code. 3) Ensure having downloaded the right R/Python and packages versions, and run code according to order.
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Funding
The Oglesby Charitable Trust