Mutations in myeloid transcription factors and activated
signaling genes predict chronic myeloid leukemia outcomes

J 2024

Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes

PERUSINI, Maria Agustina, Daniela ŽÁČKOVÁ, TaeHyung KIM, Katia B B PAGNANO, Carolina PAVLOVSKY et. al.

Basic information

Original name

Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes

Authors

PERUSINI, Maria Agustina, Daniela ŽÁČKOVÁ (203 Czech Republic, belonging to the institution), TaeHyung KIM, Katia B B PAGNANO, Carolina PAVLOVSKY, Ivana JEŽÍŠKOVÁ (203 Czech Republic, belonging to the institution), Anežka KVETKOVÁ (703 Slovakia, belonging to the institution), Tomáš JURČEK (203 Czech Republic, belonging to the institution), Jaeyoon John KIM, Young Seok YOO, Seongyoon YI, Hyewon LEE, Kyoung Ha KIM, Myunghee CHANG, Capo-Chichi JOSE-MARIO, Jessie MEDEIROS, Andrea ARRUDA, Mark D MINDEN, Zhaolei ZHANG, Sagi ABELSON, Jiří MAYER (203 Czech Republic, belonging to the institution) and Dennis Dong Hwan KIM

Edition

Blood advances, AMSTERDAM, ELSEVIER, 2024, 2473-9529

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30205 Hematology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1182/bloodadvances.2023012127

UT WoS

001293872300001

Keywords in English

Myeloid Neoplasia

Abstract

V originále

Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) towards precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifiers genes and activated signaling/myeloid transcription factor (AS/MTF), with disease progression and treatment failure in CML patients following tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis, and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes with a limit of detection of 0.2%. A total of 70 mutations were detected in 57 (22.4%) diagnostic samples, while 64 mutations were detected in 39 (27.9%) of the follow-up samples. Carrying any mutation at initial diagnosis was associated with worse outcomes following TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with Imatinib showed higher risks of treatment failure (HR 2.53, 95% CI [1.13-5.66], p=0.0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs (2G-TKI). The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival (FFS), and progression risk. Additionally, there was an observable non-significant trend indicating a heightened risk of progression to advanced disease and worse overall survival (OS). Conclusion: Mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression, even from initial diagnosis, and may help upfront TKI selection.

Citovat

PERUSINI, Maria Agustina, Daniela ŽÁČKOVÁ, TaeHyung KIM, Katia B B PAGNANO, Carolina PAVLOVSKY, Ivana JEŽÍŠKOVÁ, Anežka KVETKOVÁ, Tomáš JURČEK, Jaeyoon John KIM, Young Seok YOO, Seongyoon YI, Hyewon LEE, Kyoung Ha KIM, Myunghee CHANG, Capo-Chichi JOSE-MARIO, Jessie MEDEIROS, Andrea ARRUDA, Mark D MINDEN, Zhaolei ZHANG, Sagi ABELSON, Jiří MAYER and Dennis Dong Hwan KIM. Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes. Blood advances. AMSTERDAM: ELSEVIER, 2024, vol. 8, No 10, p. 2361-2372. ISSN 2473-9529. Available from: https://dx.doi.org/10.1182/bloodadvances.2023012127.

@article{2387637,
   author = {Perusini, Maria Agustina and Žáčková, Daniela and Kim, TaeHyung and Pagnano, Katia B B and Pavlovsky, Carolina and Ježíšková, Ivana and Kvetková, Anežka and Jurček, Tomáš and Kim, Jaeyoon John and Yoo, Young Seok and Yi, Seongyoon and Lee, Hyewon and Kim, Kyoung Ha and Chang, Myunghee and JoseandMario, CapoandChichi and Medeiros, Jessie and Arruda, Andrea and Minden, Mark D and Zhang, Zhaolei and Abelson, Sagi and Mayer, Jiří and Kim, Dennis Dong Hwan},
   article_location = {AMSTERDAM},
   article_number = {10},
   doi = {http://dx.doi.org/10.1182/bloodadvances.2023012127},
   keywords = {Myeloid Neoplasia},
   language = {eng},
   issn = {2473-9529},
   journal = {Blood advances},
   title = {Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes},
   url = {https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2023012127/515202/Mutations-in-myeloid-transcription-factors-and},
   volume = {8},
   year = {2024}
}

TY  - JOUR
ID  - 2387637
AU  - Perusini, Maria Agustina - Žáčková, Daniela - Kim, TaeHyung - Pagnano, Katia B B - Pavlovsky, Carolina - Ježíšková, Ivana - Kvetková, Anežka - Jurček, Tomáš - Kim, Jaeyoon John - Yoo, Young Seok - Yi, Seongyoon - Lee, Hyewon - Kim, Kyoung Ha - Chang, Myunghee - Jose-Mario, Capo-Chichi - Medeiros, Jessie - Arruda, Andrea - Minden, Mark D - Zhang, Zhaolei - Abelson, Sagi - Mayer, Jiří - Kim, Dennis Dong Hwan
PY  - 2024
TI  - Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes
JF  - Blood advances
VL  - 8
IS  - 10
SP  - 2361-2372
EP  - 2361-2372
PB  - ELSEVIER
SN  - 24739529
KW  - Myeloid Neoplasia
UR  - https://ashpublications.org/bloodadvances/article/doi/10.1182/bloodadvances.2023012127/515202/Mutations-in-myeloid-transcription-factors-and
N2  - Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) towards precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifiers genes and activated signaling/myeloid transcription factor (AS/MTF), with disease progression and treatment failure in CML patients following tyrosine kinase inhibitor (TKI) therapy. A total of 394 CML samples were sequenced, including 254 samples collected at initial diagnosis, and 140 samples taken during follow-up. Single-molecule molecular inversion probe (smMIP)-based next-generation sequencing (NGS) was conducted targeting recurrently mutated loci in 40 genes with a limit of detection of 0.2%. A total of 70 mutations were detected in 57 (22.4%) diagnostic samples, while 64 mutations were detected in 39 (27.9%) of the follow-up samples. Carrying any mutation at initial diagnosis was associated with worse outcomes following TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with Imatinib showed higher risks of treatment failure (HR 2.53, 95% CI [1.13-5.66], p=0.0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs (2G-TKI). The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival (FFS), and progression risk. Additionally, there was an observable non-significant trend indicating a heightened risk of progression to advanced disease and worse overall survival (OS). Conclusion: Mutations in the AS/MTF genes using smMIP-based NGS can help identify patients with a potential risk of both treatment failure and progression, even from initial diagnosis, and may help upfront TKI selection.
ER  -

PERUSINI, Maria Agustina, Daniela ŽÁČKOVÁ, TaeHyung KIM, Katia B B PAGNANO, Carolina PAVLOVSKY, Ivana JEŽÍŠKOVÁ, Anežka KVETKOVÁ, Tomáš JURČEK, Jaeyoon John KIM, Young Seok YOO, Seongyoon YI, Hyewon LEE, Kyoung Ha KIM, Myunghee CHANG, Capo-Chichi JOSE-MARIO, Jessie MEDEIROS, Andrea ARRUDA, Mark D MINDEN, Zhaolei ZHANG, Sagi ABELSON, Jiří MAYER and Dennis Dong Hwan KIM. Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes. \textit{Blood advances}. AMSTERDAM: ELSEVIER, 2024, vol.~8, No~10, p.~2361-2372. ISSN~2473-9529. Available from: https://dx.doi.org/10.1182/bloodadvances.2023012127.

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