Genomic landscape of B-other acute lymphoblastic leukemia in an
adult retrospective cohort with a focus on BCR-ABL1-like
subtype

J 2021

Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype

HRABOVSKÝ, Štěpán, Zuzana VRZALOVÁ, Jiří ŠTIKA, H. JELINKOVA, Marie JAROŠOVÁ et. al.

Základní údaje

Originální název

Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype

Autoři

HRABOVSKÝ, Štěpán (203 Česká republika, domácí), Zuzana VRZALOVÁ (203 Česká republika, domácí), Jiří ŠTIKA (203 Česká republika, domácí), H. JELINKOVA, Marie JAROŠOVÁ (203 Česká republika, domácí), Veronika NAVRKALOVÁ (203 Česká republika, domácí), Jiří MARTENEK (203 Česká republika, domácí), František FOLBER (203 Česká republika, domácí), C. SALEK, JM. HORACEK, Šárka POSPÍŠILOVÁ (203 Česká republika, garant, domácí), Jiří MAYER (203 Česká republika, domácí) a Michael DOUBEK (203 Česká republika, domácí)

Vydání

Acta Oncologica, ABINGDON, TAYLOR & FRANCIS LTD, 2021, 0284-186X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30204 Oncology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.311

Kód RIV

RIV/00216224:14740/21:00119832

Organizační jednotka

Středoevropský technologický institut

DOI

http://dx.doi.org/10.1080/0284186X.2021.1900908

UT WoS

000631403300001

Klíčová slova anglicky

B-other acute lymphoblastic leukemia; adults; BCR-ABL1-like; IKZF1; (plus); next-generation sequencing

Štítky

14110212, podil, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 15. 10. 2024 14:07, Ing. Martina Blahová

Anotace

V originále

Introduction BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a high-risk disease with a complex genomic background. Though extensively studied, data on the frequency and mutual associations of present mutations are still incomplete in adult patients. This retrospective study aims to map the genomic landscape of B-other ALL in a cohort of adult patients with a focus on the BCR-ABL1-like ALL subtype. Methods We analyzed bone marrow and peripheral blood samples of adult B-other ALL patients treated consecutively at three major Czech teaching hospitals. Samples were analyzed by cytogenetic methods, gene expression profiling, multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS). Results Fifty-eight B-other ALL patients (not BCR-ABL1, KMT2A-rearranged, ETV6-RUNX1, TCF3-PBX1, or iAMP21) were included in the study. Median follow-up was 23.8 months. Samples from 33 patients were available for a gene expression analysis, 48.9% identified as BCR-ABL1-like ALL. Of the BCR-ABL1-like ALL cases, 18.8% harbored IGH-CRLF2 and 12.5% P2RY8-CRLF2 fusion gene. We observed a higher MRD failure rate in BCR-ABL1-like than in non-BCR-ABL1-like ALL patients after the induction treatment (50.0 vs. 13.3%, p=.05). There was a trend to worse progression-free and overall survival in the BCR-ABL1-like group, though not statistically significant. Deletions in IKZF1 gene were found in 31.3% of BCR-ABL1-like cases. Patients with concurrent IKZF1 and CDKN2A/B, PAX5 or PAR1 region deletions (IKZF1 (plus) profile) had significantly worse progression-free survival than those with sole IKZF1 deletion or IKZF1 wild-type (p=.02). NGS analysis was performed in 54 patients and identified 99 short variants in TP53, JAK2, NRAS, PAX5, CREBBP, NF1, FLT3, ATM, KRAS, RUNX1, and other genes. Seventy-five of these gene variants have not yet been described in B-cell precursor ALL to date. Conclusion This study widens existing knowledge of the BCR-ABL1-like and B-other ALL genomic landscape in the adult population, supports previous findings, and identifies a number of novel gene variants.

Návaznosti

LQ1601, projekt VaV

Název: CEITEC 2020 (Akronym: CEITEC2020)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, CEITEC 2020

MUNI/A/1595/2020, interní kód MU

Název: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VIII (Akronym: VýDiTeHeMa VIII)

Investor: Masarykova univerzita, Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VIII

NV19-03-00091, projekt VaV

Název: Komplexní prognostický a prediktivní panel pro pacienty s chronickou lymfocytární leukémií: nástroj sekvenování nové generace vhodný pro klinickou praxi i studium genetického pozadí průběhu choroby

Investor: Ministerstvo zdravotnictví ČR, Comprehensive prognostic and predictive panel for chronic lymphocytic leukemia: a next-generation sequencing tool suitable for clinical practice and study of genetic architecture behind the disease progress

TN01000013, projekt VaV

Název: Personalizovaná medicína - diagnostika a terapie

Investor: Technologická agentura ČR, Personalizovaná medicína - diagnostika a terapie

90132, velká výzkumná infrastruktura

Název: NCMG II

Citovat

HRABOVSKÝ, Štěpán, Zuzana VRZALOVÁ, Jiří ŠTIKA, H. JELINKOVA, Marie JAROŠOVÁ, Veronika NAVRKALOVÁ, Jiří MARTENEK, František FOLBER, C. SALEK, JM. HORACEK, Šárka POSPÍŠILOVÁ, Jiří MAYER a Michael DOUBEK. Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype. Acta Oncologica. ABINGDON: TAYLOR & FRANCIS LTD, 2021, roč. 60, č. 6, s. 760-770. ISSN 0284-186X. Dostupné z: https://dx.doi.org/10.1080/0284186X.2021.1900908.

@article{1782159,
   author = {Hrabovský, Štěpán and Vrzalová, Zuzana and Štika, Jiří and Jelinkova, H. and Jarošová, Marie and Navrkalová, Veronika and Martenek, Jiří and Folber, František and Salek, C. and Horacek, JM. and Pospíšilová, Šárka and Mayer, Jiří and Doubek, Michael},
   article_location = {ABINGDON},
   article_number = {6},
   doi = {http://dx.doi.org/10.1080/0284186X.2021.1900908},
   keywords = {B-other acute lymphoblastic leukemia; adults; BCR-ABL1-like; IKZF1; (plus); next-generation sequencing},
   language = {eng},
   issn = {0284-186X},
   journal = {Acta Oncologica},
   title = {Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype},
   url = {https://www.tandfonline.com/doi/full/10.1080/0284186X.2021.1900908},
   volume = {60},
   year = {2021}
}

TY  - JOUR
ID  - 1782159
AU  - Hrabovský, Štěpán - Vrzalová, Zuzana - Štika, Jiří - Jelinkova, H. - Jarošová, Marie - Navrkalová, Veronika - Martenek, Jiří - Folber, František - Salek, C. - Horacek, JM. - Pospíšilová, Šárka - Mayer, Jiří - Doubek, Michael
PY  - 2021
TI  - Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype
JF  - Acta Oncologica
VL  - 60
IS  - 6
SP  - 760-770
EP  - 760-770
PB  - TAYLOR & FRANCIS LTD
SN  - 0284186X
KW  - B-other acute lymphoblastic leukemia
KW  - adults
KW  - BCR-ABL1-like
KW  - IKZF1
KW  - (plus)
KW  - next-generation sequencing
UR  - https://www.tandfonline.com/doi/full/10.1080/0284186X.2021.1900908
N2  - Introduction BCR-ABL1-like acute lymphoblastic leukemia (ALL) is a high-risk disease with a complex genomic background. Though extensively studied, data on the frequency and mutual associations of present mutations are still incomplete in adult patients. This retrospective study aims to map the genomic landscape of B-other ALL in a cohort of adult patients with a focus on the BCR-ABL1-like ALL subtype. Methods We analyzed bone marrow and peripheral blood samples of adult B-other ALL patients treated consecutively at three major Czech teaching hospitals. Samples were analyzed by cytogenetic methods, gene expression profiling, multiplex ligation-dependent probe amplification (MLPA), and next-generation sequencing (NGS). Results Fifty-eight B-other ALL patients (not BCR-ABL1, KMT2A-rearranged, ETV6-RUNX1, TCF3-PBX1, or iAMP21) were included in the study. Median follow-up was 23.8 months. Samples from 33 patients were available for a gene expression analysis, 48.9% identified as BCR-ABL1-like ALL. Of the BCR-ABL1-like ALL cases, 18.8% harbored IGH-CRLF2 and 12.5% P2RY8-CRLF2 fusion gene. We observed a higher MRD failure rate in BCR-ABL1-like than in non-BCR-ABL1-like ALL patients after the induction treatment (50.0 vs. 13.3%, p=.05). There was a trend to worse progression-free and overall survival in the BCR-ABL1-like group, though not statistically significant. Deletions in IKZF1 gene were found in 31.3% of BCR-ABL1-like cases. Patients with concurrent IKZF1 and CDKN2A/B, PAX5 or PAR1 region deletions (IKZF1 (plus) profile) had significantly worse progression-free survival than those with sole IKZF1 deletion or IKZF1 wild-type (p=.02). NGS analysis was performed in 54 patients and identified 99 short variants in TP53, JAK2, NRAS, PAX5, CREBBP, NF1, FLT3, ATM, KRAS, RUNX1, and other genes. Seventy-five of these gene variants have not yet been described in B-cell precursor ALL to date. Conclusion This study widens existing knowledge of the BCR-ABL1-like and B-other ALL genomic landscape in the adult population, supports previous findings, and identifies a number of novel gene variants.
ER  -

HRABOVSKÝ, Štěpán, Zuzana VRZALOVÁ, Jiří ŠTIKA, H. JELINKOVA, Marie JAROŠOVÁ, Veronika NAVRKALOVÁ, Jiří MARTENEK, František FOLBER, C. SALEK, JM. HORACEK, Šárka POSPÍŠILOVÁ, Jiří MAYER a Michael DOUBEK. Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype. \textit{Acta Oncologica}. ABINGDON: TAYLOR \&{}amp; FRANCIS LTD, 2021, roč.~60, č.~6, s.~760-770. ISSN~0284-186X. Dostupné z: https://dx.doi.org/10.1080/0284186X.2021.1900908.

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