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Int. J. Mol. Sci. 2019, 20(3), 789; https://doi.org/10.3390/ijms20030789

Clonal Hematopoiesis with Oncogenic Potential (CHOP): Separation from CHIP and Roads to AML

1
Department of Internal Medicine I, Division of Hematology & Hemostaseology, Medical University of Vienna, 1090 Vienna, Austria
2
Ludwig Boltzmann Institute for Hematology & Oncology, Medical University of Vienna, 1090 Vienna, Austria
3
MLL Munich Leukemia Laboratory, 81377 Munich, Germany
4
Central Institute of Medical and Chemical Laboratory Diagnostics, University Hospital Innsbruck, 6020 Innsbruck, Austria
5
Department of Laboratory Medicine, Medical University of Vienna, 1090 Vienna, Austria
6
Institute of Pathology, Paracelsus Medical University, zip code Salzburg, Austria
7
3rd Medical Department, Hanusch Hospital, 1140 Vienna, Austria
8
Department of Hematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, 40204 Düsseldorf, Germany
9
Department of Hematology and Oncology, University Medical Centre Mannheim, University of Heidelberg, 68167 Mannheim, Germany
10
Department of Hematology and Oncology, Medical University Innsbruck, 6020 Innsbruck, Austria
11
Medical Clinic 3, University Clinic Bonn (UKB Bonn), 53127 Bonn, Germany
12
Laboratory of Hematology, Pitié-Salpêtrière Hospital, 75013 Paris, France
13
Institute of Pathology, Ludwig-Maximilians University, 80539 Munich, Germany
*
Author to whom correspondence should be addressed.
Received: 21 January 2019 / Revised: 10 February 2019 / Accepted: 11 February 2019 / Published: 12 February 2019
(This article belongs to the Special Issue Genetics, Biology, and Treatment of Acute Myeloid Leukemia)
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Abstract

The development of leukemia is a step-wise process that is associated with molecular diversification and clonal selection of neoplastic stem cells. Depending on the number and combinations of lesions, one or more sub-clones expand/s after a variable latency period. Initial stages may develop early in life or later in adulthood and include premalignant (indolent) stages and the malignant phase, defined by an acute leukemia. We recently proposed a cancer model in which the earliest somatic lesions are often age-related early mutations detectable in apparently healthy individuals and where additional oncogenic mutations will lead to the development of an overt neoplasm that is usually a preleukemic condition such as a myelodysplastic syndrome. These neoplasms may or may not transform to overt acute leukemia over time. Thus, depending on the type and number of somatic mutations, clonal hematopoiesis (CH) can be divided into CH with indeterminate potential (CHIP) and CH with oncogenic potential (CHOP). Whereas CHIP mutations per se usually create the molecular background of a neoplastic process, CHOP mutations are disease-related or even disease-specific lesions that trigger differentiation and/or proliferation of neoplastic cells. Over time, the acquisition of additional oncogenic events converts preleukemic neoplasms into secondary acute myeloid leukemia (sAML). In the present article, recent developments in the field are discussed with a focus on CHOP mutations that lead to distinct myeloid neoplasms, their role in disease evolution, and the impact of additional lesions that can drive a preleukemic neoplasm into sAML. View Full-Text
Keywords: premalignant states; neoplastic stem cells; clonal evolution; cancer premalignant states; neoplastic stem cells; clonal evolution; cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Valent, P.; Kern, W.; Hoermann, G.; Milosevic Feenstra, J.D.; Sotlar, K.; Pfeilstöcker, M.; Germing, U.; Sperr, W.R.; Reiter, A.; Wolf, D.; Arock, M.; Haferlach, T.; Horny, H.-P. Clonal Hematopoiesis with Oncogenic Potential (CHOP): Separation from CHIP and Roads to AML. Int. J. Mol. Sci. 2019, 20, 789.

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