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Clinical impacts of copy number variations in B-cell differentiation and cell cycle control genes in pediatric B-cell acute lymphoblastic leukemia: a single centre experience

Klementina Crepinsek

Klementina Crepinsek

  • Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Crepinsek, Klementina
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Gasper Marinsek

Gasper Marinsek

Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
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Marinsek, Gasper
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Marko Kavcic

Marko Kavcic

  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
  • Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
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Kavcic, Marko
, 
Tomaž Prelog

Tomaž Prelog

Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
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Prelog, Tomaž
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Lidija Kitanovski

Lidija Kitanovski

Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
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Kitanovski, Lidija
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Janez Jazbec

Janez Jazbec

  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
  • Department of Oncology and Haematology, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
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Jazbec, Janez
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Marusa Debeljak

Marusa Debeljak

  • Clinical Institute for Special Laboratory Diagnostics, University Children’s Hospital, University Medical Centre LjubljanaLjubljana, Slovenia
  • Faculty of Medicine, University of LjubljanaLjubljana, Slovenia
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Debeljak, Marusa
  
22 dic 2021
Clinical impacts of copy number variations in B-cell differentiation and cell cycle control genes in pediatric B-cell acute lymphoblastic leukemia: a single centre experience's Cover Image
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Categoria dell'articolo: Research Article
Pubblicato online: 22 dic 2021
Pagine: 92 - 101
Ricevuto: 07 set 2021
Accettato: 05 nov 2021
DOI: https://doi.org/10.2478/raon-2021-0050
Parole chiave
© 2022 Klementina Crepinsek, Gasper Marinsek, Marko Kavcic, Tomaž Prelog, Lidija Kitanovski, Janez Jazbec, Marusa Debeljak, published by Sciendo
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Figure 1

Prevalence of ALL subtypes in the Slovenian pediatric B-ALL cohort.
Prevalence of ALL subtypes in the Slovenian pediatric B-ALL cohort.

Figure 2

Primary genetic alterations in patients with IKZF1 deletions.
Primary genetic alterations in patients with IKZF1 deletions.

Figure 3

The number of CNVs present in Slovenian B-ALL samples.
The number of CNVs present in Slovenian B-ALL samples.

Figure 4

Frequency of copy number variations: (A) Gene deletions in the cohort. (B) Gene amplifications in the cohort. BTG1 = BTG anti-proliferation factor 1; CDKN2A/2B = cyclin dependent kinase inhibitor 2A/2B; CRLF2 = cytokine receptor-like factor 2; CSF2RA = colony-stimulating factor 2 receptor α subunit; EBF1 = early B-cell factor 1; ETV6 = ETS variant 6; IKZF1 = IKAROS family zinc finger 1; IL3RA = interleukin 3 receptor subunit α; JAK2 = Janus kinase 2; PAX5 = paired box 5; P2RY8 = purinergic receptor P2Y8; SHOX = short-stature homeobox gene; RB1 = RB transcriptional corepressor 1
Frequency of copy number variations: (A) Gene deletions in the cohort. (B) Gene amplifications in the cohort. BTG1 = BTG anti-proliferation factor 1; CDKN2A/2B = cyclin dependent kinase inhibitor 2A/2B; CRLF2 = cytokine receptor-like factor 2; CSF2RA = colony-stimulating factor 2 receptor α subunit; EBF1 = early B-cell factor 1; ETV6 = ETS variant 6; IKZF1 = IKAROS family zinc finger 1; IL3RA = interleukin 3 receptor subunit α; JAK2 = Janus kinase 2; PAX5 = paired box 5; P2RY8 = purinergic receptor P2Y8; SHOX = short-stature homeobox gene; RB1 = RB transcriptional corepressor 1

Figure 5

(A) Event-free survival in patients with or without IKZF1 deletions (5-year event-free survival [EFS] 54.8% vs. 85.9%, p = 0.016). (B) Overall survival in patients with or without IKZF1 deletions (5-year overall survival [OS] 81.5% vs. 93.0%, p = 0.295).
(A) Event-free survival in patients with or without IKZF1 deletions (5-year event-free survival [EFS] 54.8% vs. 85.9%, p = 0.016). (B) Overall survival in patients with or without IKZF1 deletions (5-year overall survival [OS] 81.5% vs. 93.0%, p = 0.295).

Figure 6

(A) Event-free survival in patients without IKZF1 deletions, with IKZF1 deletions only, and those with the IKZF1plus profile (5-year EFS 85.9% vs. 75.0% vs. 50.8%, p = 0.049). (B) Overall survival in patients without IKZF1 deletions, with IKZF1 deletions only and those with the IKZF1plus profile (5-year OS 93.0% vs. 100% vs. 76.2%, p = 0.290).
(A) Event-free survival in patients without IKZF1 deletions, with IKZF1 deletions only, and those with the IKZF1plus profile (5-year EFS 85.9% vs. 75.0% vs. 50.8%, p = 0.049). (B) Overall survival in patients without IKZF1 deletions, with IKZF1 deletions only and those with the IKZF1plus profile (5-year OS 93.0% vs. 100% vs. 76.2%, p = 0.290).

The demographic and clinical characteristics of Slovenian B-ALL patients included in the study

Characteristic
Nr. of patients 99
Sex
Male 54 (54.5%)
Female 45 (45.5%)
Primary genetic abnormalities
ETV6-RUNX1 28 (28.3%)
BCR-ABL1 7 (7.1%)
KMTrearrangements 2A 4 (4.0%)
TCF3-PBX1 4 (4.0%)
Hyperdiploidy 27 (27.3%)
Hypodiploidy 3 (3.0%)
iAMP21 2 (2.0%)
No abnormalities recurrent Age at diagnosis 24 (24.2%)
< 1 3 (3.0%)
1–5 57 (57.6%)
≥ 6 Risk group 39 (39.4%)
Standard risk 17 (17.2%)
Intermediate risk 59 (59.6%)
High risk 23 (23.2%)
FC- minimal residual disease
Day 15
< 0.1% 35 (35.4%)
0.1–10% 48 (48.5%)
> 10% 13 (13.1%)
Unknown 3 (3.0%)
Day 33
< 0.01% 73 (73.7%)
0.01–1% 20 (20.2%)
> 1% 3 (3.0%)
Unknown 3 (3.0%)

Patients’ characteristics and response to treatment according to IKZF1 deletion status in 91 Slovenian pediatric B-ALL patients

Characteristic IKZF1 status
No IKZF1 deletion IKZF1 deletion only IKZF1plus
Nr. of patients 72 5 11
Sex
Male 34 (47.2%) 5 (100%) 9 (81.8%)
Female 38 (52.8%) 0 (0.0%) 2 (18.2%)
Primary genetic abnormalities
ETV6-RUNX1 24 (33.3%) 0 (0.0%) 1 (9.1%)
BCR-ABL1 1 (1.4%) 2 (40.0%) 4 (36.4%)
KMT2A rearrangements 4 (5.6%) 0 (0.0%) 0 (0.0%)
TCF3-PBX1 3 (4.2%) 0 (0.0%) 1 (9.1%)
Hyperdiploidy 20 (27.8%) 2 (40.0%) 1 (9.1%)
Hypodiploidy 2 (2.8%) 0 (0.0%) 1 (9.1%)
iAMP21 1 (1.4%) 0 (0.0%) 0 (0.0%)
No recurrent abnormalities 18 (25.0%) 1 (20.0%) 3 (27.3%)
Age at diagnosis
< 1 3 (4.2%) 0 (0.0%) 0 (0.0%)
1–5 41 (56.9%) 2 (40.0%) 5 (45.5%)
≥ 6 28 (38.9%) 3 (60.0%) 6 (54.5%)
Risk group
Standard risk 13 (18.1%) 0 (0.0%) 0 (0.0%)
Intermediate risk 46 (63.9%) 2 (40.0%) 4 (36.4%)
High risk 13 (18.1%) 3 (60.0%) 7 (63.6%)
FC- minimal residual disease
Day 15
< 0.1% 30 (41.7%) 0 (0.0%) 1 (9.1%)
0.1–10% 33 (45.8%) 2 (40.0%) 6 (54.5%)
> 10% 6 (8.3%) 3 (60.0%) 4 (36.4%)
Unknown 3 (4.2%) 0 (0.0%) 0 (0.0%)
Day 33
< 0.01% 56 (77.8%) 0 (0.0%) 8 (72.7%)
0.01–1% 13 (18.1%) 3 (60.0%) 2 (18.2%)
> 1% 2 (2.8%) 1 (20.0%) 0 (0.0%)
Unknown 1 (1.4%) 1 (20.0%) 1 (9.1%)
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