Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

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

MA. Perusini, D. Žáčková, T. Kim, K. Pagnano, C. Pavlovsky, I. Ježíšková, A. Kvetková, T. Jurček, J. Kim, Y. Yoo, S. Yi, H. Lee, KH. Kim, M. Chang, JM. Capo-Chichi, JJF. Medeiros, A. Arruda, M. Minden, Z. Zhang, S. Abelson, J. Mayer, DD. Hwan Kim

. 2024 ; 8 (10) : 2361-2372. [pub] 20240528

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc24013857

Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after 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%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In 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 and may help upfront TKI selection.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc24013857
003      
CZ-PrNML
005      
20240905134333.0
007      
ta
008      
240725s2024 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1182/bloodadvances.2023012127 $2 doi
035    __
$a (PubMed)38447114
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Perusini, Maria Agustina $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
245    10
$a Mutations in myeloid transcription factors and activated signaling genes predict chronic myeloid leukemia outcomes / $c MA. Perusini, D. Žáčková, T. Kim, K. Pagnano, C. Pavlovsky, I. Ježíšková, A. Kvetková, T. Jurček, J. Kim, Y. Yoo, S. Yi, H. Lee, KH. Kim, M. Chang, JM. Capo-Chichi, JJF. Medeiros, A. Arruda, M. Minden, Z. Zhang, S. Abelson, J. Mayer, DD. Hwan Kim
520    9_
$a Advancements in genomics are transforming the clinical management of chronic myeloid leukemia (CML) toward precision medicine. The impact of somatic mutations on treatment outcomes is still under debate. We studied the association of somatic mutations in epigenetic modifier genes and activated signaling/myeloid transcription factors (AS/MTFs) with disease progression and treatment failure in patients with CML after 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%. Seventy mutations were detected in 57 diagnostic samples (22.4%), whereas 64 mutations were detected in 39 of the follow-up samples (27.9%). Carrying any mutation at initial diagnosis was associated with worse outcomes after TKI therapy, particularly in AS/MTF genes. Patients having these mutations at initial diagnosis and treated with imatinib showed higher risks of treatment failure (hazard ratio, 2.53; 95% confidence interval, 1.13-5.66; P = .0239). The adverse prognostic impact of the mutations was not clear for patients treated with second-generation TKIs. The multivariate analysis affirmed that mutations in AS/MTF genes independently serve as adverse prognostic factors for molecular response, failure-free survival, and progression risk. Additionally, there was an observable nonsignificant trend indicating a heightened risk of progression to advanced disease and worse overall survival. In 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 and may help upfront TKI selection.
650    _2
$a lidé $7 D006801
650    12
$a chronická myeloidní leukemie $x genetika $x farmakoterapie $x mortalita $x diagnóza $7 D015464
650    12
$a mutace $7 D009154
650    _2
$a mužské pohlaví $7 D008297
650    _2
$a lidé středního věku $7 D008875
650    _2
$a ženské pohlaví $7 D005260
650    _2
$a dospělí $7 D000328
650    _2
$a senioři $7 D000368
650    _2
$a signální transdukce $7 D015398
650    _2
$a inhibitory proteinkinas $x terapeutické užití $7 D047428
650    _2
$a prognóza $7 D011379
650    _2
$a transkripční faktory $x genetika $7 D014157
650    _2
$a výsledek terapie $7 D016896
650    _2
$a vysoce účinné nukleotidové sekvenování $7 D059014
650    _2
$a mladý dospělý $7 D055815
650    _2
$a senioři nad 80 let $7 D000369
650    _2
$a progrese nemoci $7 D018450
655    _2
$a časopisecké články $7 D016428
700    1_
$a Žáčková, Daniela $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Brno, Czech Republic $1 https://orcid.org/0000000198028148 $7 xx0074334
700    1_
$a Kim, Taehyung $u Department of Computer Science, University of Toronto, Toronto, ON, Canada $u The Donnelly Centre for Cellular and Biomolecular Research, Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada
700    1_
$a Pagnano, Katia $u Hematology and Hemotherapy Center, University of Campinas, Campinas, Brazil $1 https://orcid.org/0000000179750805
700    1_
$a Pavlovsky, Carolina $u Fundaleu, Buenos Aires, Argentina
700    1_
$a Ježíšková, Ivana $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Brno, Czech Republic $1 https://orcid.org/0000000187607718 $7 mzk2005318075
700    1_
$a Kvetková, Anežka $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Brno, Czech Republic
700    1_
$a Jurček, Tomáš $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Brno, Czech Republic
700    1_
$a Kim, Jaeyoon $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
700    1_
$a Yoo, Youngseok $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
700    1_
$a Yi, Seongyoon $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Department of Internal Medicine, Inje University Ilsan-Paik Hospital, Goyang, Republic of Korea
700    1_
$a Lee, Hyewon $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Department of Internal Medicine, Center for Hematologic Malignancies, National Cancer Center, Goyang, Republic of Korea
700    1_
$a Kim, Kyoung Ha $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Division of Hematology and Oncology, Department of Internal Medicine, Soon Chun Hyang University Seoul Hospital, Seoul, Republic of Korea
700    1_
$a Chang, Myunghee $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u National Health Insurance Service Ilsan Hospital, Ilsan, Republic of Korea
700    1_
$a Capo-Chichi, Jose-Mario $u Genome Diagnostics & Cancer Cytogenetics Laboratories, Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, Canada $1 https://orcid.org/0000000274403633
700    1_
$a Medeiros, Jessie J F $u Ontario Institute for Cancer Research, Toronto, ON, Canada $u Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada $1 https://orcid.org/0000000165974613
700    1_
$a Arruda, Andrea $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Malignant Hematology Tissue Bank, Princess Margaret Cancer Centre, Toronto, ON, Canada
700    1_
$a Minden, Mark $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Malignant Hematology Tissue Bank, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Faculty of Medicine, University of Toronto, Toronto, ON, Canada $1 https://orcid.org/0000000290898816
700    1_
$a Zhang, Zhaolei $u The Donnelly Centre for Cellular and Biomolecular Research, Donnelly Centre for Cellular & Biomolecular Research, Toronto, ON, Canada $u Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada $u Department of Computer Science, University of Toronto, Toronto, ON, Canada
700    1_
$a Abelson, Sagi $u Ontario Institute for Cancer Research, Toronto, ON, Canada $u Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada $1 https://orcid.org/0000000317473819
700    1_
$a Mayer, Jiri $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Brno, Czech Republic
700    1_
$a Hwan Kim, Dennis Dong $u Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada $u Faculty of Medicine, University of Toronto, Toronto, ON, Canada
773    0_
$w MED00194912 $t Blood advances $x 2473-9537 $g Roč. 8, č. 10 (2024), s. 2361-2372
856    41
$u https://pubmed.ncbi.nlm.nih.gov/38447114 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y - $z 0
990    __
$a 20240725 $b ABA008
991    __
$a 20240905134327 $b ABA008
999    __
$a ok $b bmc $g 2143581 $s 1225723
BAS    __
$a 3
BAS    __
$a PreBMC-MEDLINE
BMC    __
$a 2024 $b 8 $c 10 $d 2361-2372 $e 20240528 $i 2473-9537 $m Blood advances $n Blood Adv $x MED00194912
LZP    __
$a Pubmed-20240725

Najít záznam

Citační ukazatele

Možnosti archivace