KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders
<i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell...
Ausführliche Beschreibung
Autor*in: |
Elena Vendramini [verfasserIn] Riccardo Bomben [verfasserIn] Federico Pozzo [verfasserIn] Tamara Bittolo [verfasserIn] Erika Tissino [verfasserIn] Valter Gattei [verfasserIn] Antonella Zucchetto [verfasserIn] |
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Format: |
E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2022 |
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Übergeordnetes Werk: |
In: Cancers - MDPI AG, 2010, 14(2022), 3, p 666 |
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Übergeordnetes Werk: |
volume:14 ; year:2022 ; number:3, p 666 |
Links: |
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DOI / URN: |
10.3390/cancers14030666 |
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Katalog-ID: |
DOAJ013413716 |
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10.3390/cancers14030666 doi (DE-627)DOAJ013413716 (DE-599)DOAJa786f2805e1e4cf48301d89f8c0188da DE-627 ger DE-627 rakwb eng RC254-282 Elena Vendramini verfasserin aut KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. KRAS RAS-MAPK pathway RAS/RAF/MEK/ERK inhibitors mature B cell lymphoproliferative disorders Neoplasms. Tumors. Oncology. Including cancer and carcinogens Riccardo Bomben verfasserin aut Federico Pozzo verfasserin aut Tamara Bittolo verfasserin aut Erika Tissino verfasserin aut Valter Gattei verfasserin aut Antonella Zucchetto verfasserin aut In Cancers MDPI AG, 2010 14(2022), 3, p 666 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:3, p 666 https://doi.org/10.3390/cancers14030666 kostenfrei https://doaj.org/article/a786f2805e1e4cf48301d89f8c0188da kostenfrei https://www.mdpi.com/2072-6694/14/3/666 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 3, p 666 |
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10.3390/cancers14030666 doi (DE-627)DOAJ013413716 (DE-599)DOAJa786f2805e1e4cf48301d89f8c0188da DE-627 ger DE-627 rakwb eng RC254-282 Elena Vendramini verfasserin aut KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. KRAS RAS-MAPK pathway RAS/RAF/MEK/ERK inhibitors mature B cell lymphoproliferative disorders Neoplasms. Tumors. Oncology. Including cancer and carcinogens Riccardo Bomben verfasserin aut Federico Pozzo verfasserin aut Tamara Bittolo verfasserin aut Erika Tissino verfasserin aut Valter Gattei verfasserin aut Antonella Zucchetto verfasserin aut In Cancers MDPI AG, 2010 14(2022), 3, p 666 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:3, p 666 https://doi.org/10.3390/cancers14030666 kostenfrei https://doaj.org/article/a786f2805e1e4cf48301d89f8c0188da kostenfrei https://www.mdpi.com/2072-6694/14/3/666 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 3, p 666 |
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10.3390/cancers14030666 doi (DE-627)DOAJ013413716 (DE-599)DOAJa786f2805e1e4cf48301d89f8c0188da DE-627 ger DE-627 rakwb eng RC254-282 Elena Vendramini verfasserin aut KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. KRAS RAS-MAPK pathway RAS/RAF/MEK/ERK inhibitors mature B cell lymphoproliferative disorders Neoplasms. Tumors. Oncology. Including cancer and carcinogens Riccardo Bomben verfasserin aut Federico Pozzo verfasserin aut Tamara Bittolo verfasserin aut Erika Tissino verfasserin aut Valter Gattei verfasserin aut Antonella Zucchetto verfasserin aut In Cancers MDPI AG, 2010 14(2022), 3, p 666 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:3, p 666 https://doi.org/10.3390/cancers14030666 kostenfrei https://doaj.org/article/a786f2805e1e4cf48301d89f8c0188da kostenfrei https://www.mdpi.com/2072-6694/14/3/666 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 3, p 666 |
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10.3390/cancers14030666 doi (DE-627)DOAJ013413716 (DE-599)DOAJa786f2805e1e4cf48301d89f8c0188da DE-627 ger DE-627 rakwb eng RC254-282 Elena Vendramini verfasserin aut KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. KRAS RAS-MAPK pathway RAS/RAF/MEK/ERK inhibitors mature B cell lymphoproliferative disorders Neoplasms. Tumors. Oncology. Including cancer and carcinogens Riccardo Bomben verfasserin aut Federico Pozzo verfasserin aut Tamara Bittolo verfasserin aut Erika Tissino verfasserin aut Valter Gattei verfasserin aut Antonella Zucchetto verfasserin aut In Cancers MDPI AG, 2010 14(2022), 3, p 666 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:3, p 666 https://doi.org/10.3390/cancers14030666 kostenfrei https://doaj.org/article/a786f2805e1e4cf48301d89f8c0188da kostenfrei https://www.mdpi.com/2072-6694/14/3/666 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 3, p 666 |
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10.3390/cancers14030666 doi (DE-627)DOAJ013413716 (DE-599)DOAJa786f2805e1e4cf48301d89f8c0188da DE-627 ger DE-627 rakwb eng RC254-282 Elena Vendramini verfasserin aut KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier <i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. KRAS RAS-MAPK pathway RAS/RAF/MEK/ERK inhibitors mature B cell lymphoproliferative disorders Neoplasms. Tumors. Oncology. Including cancer and carcinogens Riccardo Bomben verfasserin aut Federico Pozzo verfasserin aut Tamara Bittolo verfasserin aut Erika Tissino verfasserin aut Valter Gattei verfasserin aut Antonella Zucchetto verfasserin aut In Cancers MDPI AG, 2010 14(2022), 3, p 666 (DE-627)614095670 (DE-600)2527080-1 20726694 nnns volume:14 year:2022 number:3, p 666 https://doi.org/10.3390/cancers14030666 kostenfrei https://doaj.org/article/a786f2805e1e4cf48301d89f8c0188da kostenfrei https://www.mdpi.com/2072-6694/14/3/666 kostenfrei https://doaj.org/toc/2072-6694 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2005 GBV_ILN_2009 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2055 GBV_ILN_2111 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 14 2022 3, p 666 |
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KRAS and RAS-MAPK Pathway Deregulation in Mature B Cell Lymphoproliferative Disorders |
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<i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. |
abstractGer |
<i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. |
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<i<KRAS</i< mutations account for the most frequent mutations in human cancers, and are generally correlated with disease aggressiveness, poor prognosis, and poor response to therapies. KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology. |
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KRAS is required for adult hematopoiesis and plays a key role in B cell development and mature B cell proliferation and survival, proved to be critical for B cell receptor-induced ERK pathway activation. In mature B cell neoplasms, commonly seen in adults, KRAS and RAS-MAPK pathway aberrations occur in a relevant fraction of patients, reaching high recurrence in some specific subtypes like multiple myeloma and hairy cell leukemia. As inhibitors targeting the RAS-MAPK pathway are being developed and improved, it is of outmost importance to precisely identify all subgroups of patients that could potentially benefit from their use. Herein, we review the role of KRAS and RAS-MAPK signaling in malignant hematopoiesis, focusing on mature B cell lymphoproliferative disorders. We discuss KRAS and RAS-MAPK pathway aberrations describing type, incidence, mutual exclusion with other genetic abnormalities, and association with prognosis. We review the current therapeutic strategies applied in mature B cell neoplasms to counteract RAS-MAPK signaling in pre-clinical and clinical studies, including most promising combination therapies. We finally present an overview of genetically engineered mouse models bearing KRAS and RAS-MAPK pathway aberrations in the hematopoietic compartment, which are valuable tools in the understanding of cancer biology and etiology.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">KRAS</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">RAS-MAPK pathway</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">RAS/RAF/MEK/ERK inhibitors</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">mature B cell lymphoproliferative disorders</subfield></datafield><datafield tag="653" ind1=" " ind2="0"><subfield code="a">Neoplasms. Tumors. Oncology. 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