THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION

Therapy-related Myeloid Neoplasm (t-MN) represents one of the worst long-term consequences of cytotoxic therapy for primary tumors and autoimmune disease. Poor survival and refractoriness to current treatment strategies characterize affected patients from a clinical point of view. In our aging soci...

Full description

Bibliographic Details
Main Authors: Emiliano Fabiani, Giulia Falconi, Antonio Cristiano, H. Hajrullaj, Giuseppe Leone, Maria Teresa Voso
Format: Article
Language:English
Published: Mattioli1885 2023-10-01
Series:Mediterranean Journal of Hematology and Infectious Diseases
Online Access:http://www.mjhid.org/index.php/mjhid/article/view/5496
_version_ 1797644647693025280
author Emiliano Fabiani
Giulia Falconi
Antonio Cristiano
H. Hajrullaj
Giulia Falconi
Giuseppe Leone
Maria Teresa Voso
author_facet Emiliano Fabiani
Giulia Falconi
Antonio Cristiano
H. Hajrullaj
Giulia Falconi
Giuseppe Leone
Maria Teresa Voso
author_sort Emiliano Fabiani
collection DOAJ
description Therapy-related Myeloid Neoplasm (t-MN) represents one of the worst long-term consequences of cytotoxic therapy for primary tumors and autoimmune disease. Poor survival and refractoriness to current treatment strategies characterize affected patients from a clinical point of view. In our aging societies, where newer therapies and ameliorated cancer management protocols are improving the life expectancy of cancer patients, therapy-related Myeloid Neoplasms are an emerging problem. Although several research groups have contributed to characterizing the main risk factors in t-MN development, the multiplicity of primary tumors, in association with the different therapeutic strategies available and the new drugs in development, make interpreting the current data still complex. The main risk factors involved in t-MN pathogenesis can be subgrouped into patient-specific, inherited, and acquired predispositions.  Although t-MN can occur at any age, the risk tends to increase with advancing age, and older patients, characterized by a higher number of comorbidities, are more likely to develop the disease. Thanks to the availability of deep sequencing techniques, germline variants have been reported in 15-20% of t-MN patients, highlighting their role in cancer predisposition. It is becoming increasingly evident that t-MN with driver gene mutations may arise in the background of Clonal Hematopoiesis of Indeterminate Potential (CHIP) under the positive selective pressure of chemo and/or radiation therapies. Although CHIP is generally considered benign, it has been associated with an increased risk of t-MN. In this context, the phenomenon of clonal evolution may be described as a dynamic process of expansion of preexisting clones, with or without acquisition of additional genetic alterations, that, by favoring the proliferation of more aggressive and/or resistant clones, may play a crucial role in the progression from preleukemic states to t-MN.
first_indexed 2024-03-11T14:33:31Z
format Article
id doaj.art-a1e5b21c3713413890bb5933b2b54d57
institution Directory Open Access Journal
issn 2035-3006
language English
last_indexed 2024-03-11T14:33:31Z
publishDate 2023-10-01
publisher Mattioli1885
record_format Article
series Mediterranean Journal of Hematology and Infectious Diseases
spelling doaj.art-a1e5b21c3713413890bb5933b2b54d572023-10-31T06:20:26ZengMattioli1885Mediterranean Journal of Hematology and Infectious Diseases2035-30062023-10-0115110.4084/MJHID.2023.064THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTIONEmiliano FabianiGiulia Falconi0Antonio Cristiano1H. Hajrullaj2Giulia Falconi3Giuseppe Leone4Maria Teresa VosoUniversità di Roma TorvergataUniversità di Roma TorvergataUniversità di Roma TorvergataUniversità di Roma TorvergataUniversità Cattolica del Sacro Cuore Therapy-related Myeloid Neoplasm (t-MN) represents one of the worst long-term consequences of cytotoxic therapy for primary tumors and autoimmune disease. Poor survival and refractoriness to current treatment strategies characterize affected patients from a clinical point of view. In our aging societies, where newer therapies and ameliorated cancer management protocols are improving the life expectancy of cancer patients, therapy-related Myeloid Neoplasms are an emerging problem. Although several research groups have contributed to characterizing the main risk factors in t-MN development, the multiplicity of primary tumors, in association with the different therapeutic strategies available and the new drugs in development, make interpreting the current data still complex. The main risk factors involved in t-MN pathogenesis can be subgrouped into patient-specific, inherited, and acquired predispositions.  Although t-MN can occur at any age, the risk tends to increase with advancing age, and older patients, characterized by a higher number of comorbidities, are more likely to develop the disease. Thanks to the availability of deep sequencing techniques, germline variants have been reported in 15-20% of t-MN patients, highlighting their role in cancer predisposition. It is becoming increasingly evident that t-MN with driver gene mutations may arise in the background of Clonal Hematopoiesis of Indeterminate Potential (CHIP) under the positive selective pressure of chemo and/or radiation therapies. Although CHIP is generally considered benign, it has been associated with an increased risk of t-MN. In this context, the phenomenon of clonal evolution may be described as a dynamic process of expansion of preexisting clones, with or without acquisition of additional genetic alterations, that, by favoring the proliferation of more aggressive and/or resistant clones, may play a crucial role in the progression from preleukemic states to t-MN. http://www.mjhid.org/index.php/mjhid/article/view/5496
spellingShingle Emiliano Fabiani
Giulia Falconi
Antonio Cristiano
H. Hajrullaj
Giulia Falconi
Giuseppe Leone
Maria Teresa Voso
THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION
Mediterranean Journal of Hematology and Infectious Diseases
title THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION
title_full THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION
title_fullStr THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION
title_full_unstemmed THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION
title_short THERAPY-RELATED MYELOID NEOPLASMS: PREDISPOSITION AND CLONAL EVOLUTION
title_sort therapy related myeloid neoplasms predisposition and clonal evolution
url http://www.mjhid.org/index.php/mjhid/article/view/5496
work_keys_str_mv AT emilianofabiani therapyrelatedmyeloidneoplasmspredispositionandclonalevolution
AT giuliafalconi therapyrelatedmyeloidneoplasmspredispositionandclonalevolution
AT antoniocristiano therapyrelatedmyeloidneoplasmspredispositionandclonalevolution
AT hhajrullaj therapyrelatedmyeloidneoplasmspredispositionandclonalevolution
AT giuliafalconi therapyrelatedmyeloidneoplasmspredispositionandclonalevolution
AT giuseppeleone therapyrelatedmyeloidneoplasmspredispositionandclonalevolution
AT mariateresavoso therapyrelatedmyeloidneoplasmspredispositionandclonalevolution