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.

Basic information

Original name

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

Authors

HRABOVSKÝ, Štěpán (203 Czech Republic, belonging to the institution), Zuzana VRZALOVÁ (203 Czech Republic, belonging to the institution), Jiří ŠTIKA (203 Czech Republic, belonging to the institution), H. JELINKOVA, Marie JAROŠOVÁ (203 Czech Republic, belonging to the institution), Veronika NAVRKALOVÁ (203 Czech Republic, belonging to the institution), Jiří MARTENEK (203 Czech Republic, belonging to the institution), František FOLBER (203 Czech Republic, belonging to the institution), C. SALEK, JM. HORACEK, Šárka POSPÍŠILOVÁ (203 Czech Republic, guarantor, belonging to the institution), Jiří MAYER (203 Czech Republic, belonging to the institution) and Michael DOUBEK (203 Czech Republic, belonging to the institution)

Edition

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

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30204 Oncology

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 4.311

RIV identification code

RIV/00216224:14740/21:00119832

Organization unit

Central European Institute of Technology

DOI

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

UT WoS

000631403300001

Keywords in English

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

Abstract

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.

Links

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

MUNI/A/1595/2020, interní kód MU

Name: Nové přístupy ve výzkumu, diagnostice a terapii hematologických malignit VIII (Acronym: VýDiTeHeMa VIII)

Investor: Masaryk University

NV19-03-00091, research and development project

Name: 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: Ministry of Health of the CR

TN01000013, research and development project

Name: Personalizovaná medicína - diagnostika a terapie

Investor: Technology Agency of the Czech Republic, Personalized Medicine – Diagnostics and Therapy

90132, large research infrastructures

Name: 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 and 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, vol. 60, No 6, p. 760-770. ISSN 0284-186X. Available from: 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 and 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, vol.~60, No~6, p.~760-770. ISSN~0284-186X. Available from: https://dx.doi.org/10.1080/0284186X.2021.1900908.

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