Detail
Article
Online article
FT
Medvik - BMC
  • Something wrong with this record ?

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

S. Hrabovsky, Z. Vrzalova, J. Stika, H. Jelinkova, M. Jarosova, V. Navrkalova, J. Martenek, F. Folber, C. Salek, JM. Horacek, S. Pospisilova, J. Mayer, M. Doubek

. 2021 ; 60 (6) : 760-770. [pub] 20210322

Language English Country Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc21025626

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 (IKZF1plus 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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21025626
003      
CZ-PrNML
005      
20211026133637.0
007      
ta
008      
211013s2021 xxk f 000 0|eng||
009      
AR
024    7_
$a 10.1080/0284186X.2021.1900908 $2 doi
035    __
$a (PubMed)33750258
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxk
100    1_
$a Hrabovsky, Stepan $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Faculty of Medicine, Masaryk University, Brno, Czechia $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia
245    10
$a Genomic landscape of B-other acute lymphoblastic leukemia in an adult retrospective cohort with a focus on BCR-ABL1-like subtype / $c S. Hrabovsky, Z. Vrzalova, J. Stika, H. Jelinkova, M. Jarosova, V. Navrkalova, J. Martenek, F. Folber, C. Salek, JM. Horacek, S. Pospisilova, J. Mayer, M. Doubek
520    9_
$a 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 (IKZF1plus 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.
650    _2
$a dospělí $7 D000328
650    _2
$a kohortové studie $7 D015331
650    _2
$a stanovení celkové genové exprese $7 D020869
650    _2
$a genomika $7 D023281
650    _2
$a lidé $7 D006801
650    12
$a akutní lymfatická leukemie $x genetika $7 D054198
650    _2
$a retrospektivní studie $7 D012189
655    _2
$a časopisecké články $7 D016428
700    1_
$a Vrzalova, Zuzana $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Central European Institute of Technology (CEITEC), Brno, Czechia
700    1_
$a Stika, Jiri $u Central European Institute of Technology (CEITEC), Brno, Czechia
700    1_
$a Jelinkova, Hana $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia
700    1_
$a Jarosova, Marie $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Faculty of Medicine, Masaryk University, Brno, Czechia $u Central European Institute of Technology (CEITEC), Brno, Czechia
700    1_
$a Navrkalova, Veronika $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Central European Institute of Technology (CEITEC), Brno, Czechia
700    1_
$a Martenek, Jiri $u Faculty of Medicine, Masaryk University, Brno, Czechia
700    1_
$a Folber, Frantisek $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Faculty of Medicine, Masaryk University, Brno, Czechia $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia
700    1_
$a Salek, Cyril $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia $u Institute of Hematology and Blood Transfusion, Prague, Czechia $u Institute of Clinical and Experimental Hematology, First Faculty of Medicine, Charles University, Prague, Czechia
700    1_
$a Horacek, Jan M $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia $u Fourth Department of Internal Medicine - Hematology, University Hospital Hradec Kralove, Hradec Kralove, Czechia $u Department of Military Internal Medicine and Hygiene, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czechia
700    1_
$a Pospisilova, Sarka $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Faculty of Medicine, Masaryk University, Brno, Czechia $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia $u Central European Institute of Technology (CEITEC), Brno, Czechia
700    1_
$a Mayer, Jiri $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Faculty of Medicine, Masaryk University, Brno, Czechia $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia $u Central European Institute of Technology (CEITEC), Brno, Czechia
700    1_
$a Doubek, Michael $u Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, Brno, Czechia $u Faculty of Medicine, Masaryk University, Brno, Czechia $u Czech Leukemia Study Group - for Life (CELL), Brno, Czechia $u Central European Institute of Technology (CEITEC), Brno, Czechia
773    0_
$w MED00009028 $t Acta oncologica (Stockholm, Sweden) $x 1651-226X $g Roč. 60, č. 6 (2021), s. 760-770
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33750258 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20211013 $b ABA008
991    __
$a 20211026133643 $b ABA008
999    __
$a ok $b bmc $g 1714601 $s 1146133
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 60 $c 6 $d 760-770 $e 20210322 $i 1651-226X $m Acta oncologica $n Acta Oncol $x MED00009028
LZP    __
$a Pubmed-20211013

Find record

Citation metrics

Archiving options