Oncotarget

Research Papers:

Similar expression profiles in CD34+ cells from chronic phase chronic myeloid leukemia patients with and without deep molecular responses to nilotinib

Ami B. Patel, Thoralf Lange, Anthony D. Pomicter, Christopher J. Conley, Christina A. Harrington, Kimberly R. Reynolds, Todd W. Kelley, Thomas O’Hare and Michael W. Deininger _

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Oncotarget. 2018; 9:17889-17894. https://doi.org/10.18632/oncotarget.24954

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Abstract

Ami B. Patel1,*, Thoralf Lange5,*, Anthony D. Pomicter2,*, Christopher J. Conley2, Christina A. Harrington4, Kimberly R. Reynolds2, Todd W. Kelley3, Thomas O’Hare1,2 and Michael W. Deininger1,2

1Division of Hematology and Hematologic Malignancies, The University of Utah, Salt Lake City, UT, USA

2Huntsman Cancer Institute, The University of Utah, Salt Lake City, UT, USA

3Department of Pathology, The University of Utah, Salt Lake City, UT, USA

4Integrated Genomics Laboratory, Oregon Health and Science University, Portland, OR, USA

5University of Leipzig, Division of Haematology and Oncology, Leipzig, Germany

*These authors contributed equally to this work

Correspondence to:

Michael W. Deininger, email: [email protected]

Keywords: chronic myeloid leukemia; BCR-ABL1; deep molecular response; treatment-free remission

Received: January 20, 2018     Accepted: March 15, 2018     Published: April 03, 2018

ABSTRACT

The life expectancy of patients with chronic phase chronic myeloid leukemia on tyrosine kinase inhibitor therapy now approaches that of the general population. Approximately 60% of patients treated with second generation tyrosine kinase inhibitors achieve a deep molecular response, the prerequisite for a trial of treatment-free remission. Those patients unlikely to achieve deep molecular response may benefit from more intensive therapy up front. To identify biomarkers predicting deep molecular response we performed transcriptional profiling on CD34+ progenitor cells from newly diagnosed chronic phase chronic myeloid leukemia patients treated with nilotinib on a prospective clinical trial. Using unsupervised and targeted analytical strategies, we show that gene expression profiles are similar in patients with and without subsequent deep molecular response. This result is in contrast to the distinct expression signature of CD34+ chronic phase chronic myeloid leukemia patients failing to achieve a cytogenetic response on imatinib and suggests that deep molecular response to second-generation tyrosine kinase inhibitors is governed by the biology of more primitive chronic myeloid leukemia cells or extrinsic factors.


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