The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)
Abstract
:1. Introduction
1.1. ETV6
1.2. RUNX1
1.3. Detection, Mechanism, and Clinical Significance of t(12;21)
2. Secondary Genetic Rearrangements
2.1. Chromosome 12
2.2. Chromosome 6
2.3. Chromosome 21
2.4. Chromosome 9
2.5. Chromosome 5
2.6. Chromosome 7
2.7. Chromosome 11
3. ETV6::RUNX1+ Prognosis and Treatment
4. ETV6::RUNX1+ Future Treatment Perspective
5. ETV6::RUNX1-like
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AIEOP | AssociazioneItaliana di Ematologia e OncologiaPediatrica |
AIM1 | Absent in melanoma 1 protein |
ALL | Acute lymphoblastic leukemia |
AML | Acute myeloid leukemia |
ANGPTL2 | Angiopoietin-like 2 |
ARPP21 | CAMP-regulated phosphoprotein 21 |
B-ALL | B-cell acute lymphoblastic leukemia |
BCR::ABL1 | BCR and ABL fusion gene |
BCR::ABL1-like ALL | BCR and ABL fusion gene-like acute lymphoblastic leukemia |
BFM | Berlin–Frankfurt–Münster |
BIRC7 | Baculoviral IAP repeat containing 7 |
BM | Bone marrow |
BMF | Bcl2 modifying factor |
BTG1 | BTG-anti-proliferation factor 1 |
CD95 | Cluster of differentiation 95 |
CDKN1A | Cyclin-dependent kinase inhibitor 1A |
CDKN1B | Cyclin-dependent kinase inhibitor 1B |
CLIC5 | Chloride intracellular channel 5 |
CNAs | Copy number alteration |
CNS1 | CNS1 = patients with white blood cell count in cerebrospinal fluid < 5 and having no blasts in the cerebrospinal fluid |
DLBCL | Diffuse large B-cell lymphoma |
EBF1 | EBF transcription factor 1 |
EFS | Event-free survival |
ETS | Erythroblast transformation specific |
ETV6 | ETS variant transcription factor 6 |
ETV6::RUNX1 | ETS variant transcription factor 6 and RUNX family transcription factor 1 fusion gene |
ETV6::RUNX1-like ALL | ETS variant transcription factor 6 and RUNX family transcription factor 1 fusion gene-like acute lymphoblastic leukemia |
ETV6::RUNX1+ | ETV6::RUNX1-positive |
ETV6::RUNX1− | ETV6::RUNX1-negative |
FISH | Fluorescence in situ hybridization (FISH) |
FLT3 | Fms-related receptor tyrosine kinase 3 |
FOXO3A | Forkheadbox O3 |
FPD/AML | familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML) |
FRALLE 93 | French group for childhood ALL 93 trial (FRALLE 93 |
GD-ALL-2008 | Guangdong Children’s Leukemia Group-ALL-2008 |
GDP | Guanosine diphosphate |
GIPFEL | Genomic inverse PCR for exploration of ligated breakpoints |
GTP | Bound and inactive guanosine diphosphate |
HLH | Helix loop helix |
HRAS | HRasproto-oncogene, GTPase |
HSCs | Hematopoietic stem cells |
iAMP21 | Intrachromosomal amplification of chromosome 21 |
IGF2BP | Insulin-like growth factor 2 mRNA-binding protein |
IGF2BP1 | Insulin-like growth factor 2 MRNA-Binding Protein 1 |
IGF2BP2 | Insulin-like growth factor 2 MRNA-Binding Protein 2 |
IGF2BP3 | Insulin-like growth factor 2 MRNA-Binding Protein 3 |
IGH::IL3 | Immunoglobulin heavy locus and interleukin 3 fusion gene |
IL7R | Interleukin 7 receptor |
KMT2A | lysine methyltransferase 2A |
KRAS | KRAS proto-oncogene, GTPase |
L-ASP | L-asparaginase |
MDS | Myelodysplastic syndrome |
MLL-r | mixed-lineage leukemia gene rearrangement |
MLPA | Multiplex ligation probe-dependent amplification |
MRD | Minimal residual disease |
NF1 | Neurofibromin 1 |
NGS | Next-generation sequencing |
NOPHO | Nordic Society of Pediatric Hematology and Oncology |
NR3C1 | Nuclear receptor subfamily 3 group C member 1 |
NRAS | NRAS proto-oncogene, GTPase |
OS | Overall survival |
PAX5 | Paired box 5 |
PTPN11 | Protein tyrosine phosphatase non-receptor type 11 |
PTPN11 | Protein tyrosine phosphatase non-receptor type 11 |
RAGs | Recombination-activating genes |
RAS | Protein family include |
RHD | DNA-binding Runt-domain |
RT-PCR | Reverse transcriptase-polymerase chain reaction |
RUNX1 | RUNX family transcription factor 1 |
SPI-B | Spi-B transcription factor |
SYK | Spleen tyrosine kinase |
T-ALL | T-cell acute lymphoblastic leukemia |
TCF3::HLF | Transcription factor 3 and HLF transcription factor fusion gene |
TCF3::PBX1 | Transcription factor 3 and PBX homeobox 1 |
WBC | White blood cell |
WBP1L | WW domain-binding protein 1-like |
WGS/WES | Whole genome/whole exome sequencing |
WHO-HAEM5 | 5th edition of the World Health Organization Classification of HaematolymphoidTumours |
ZFP423 | Zinc finger protein 423 |
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Chromosome Number | Observed Abnormality | Possibly Covered Genes | Frequency of Occurrence | Reference |
---|---|---|---|---|
12 | deletion of 12p | ETV6, CDKN1B, BCL2L14, BTG1, KRAS | 12–39% | [58,66,67] |
6 | deletion of 6q | AIM1, PRDM1, FOXO3, CCNC3, FYN, CDKN1A | 13–33% | [66,68] |
21 | gain of normal chromosome 21 gain of the der(21)t(12;21)(p13;q22) | RUNX1 | 25% | [61,67] |
9 | deletion of 9p | CDKN2A/B, PAX5, MTAP, JAK2, P14ARF, P16IKN4a/ARF | 10–25% | [58,66] |
5 | deletion of 5q | NR3C1, EBF1 | 23% | [69] |
3 | deletion of 3p deletion of 3q | LIMDI, ARPP-21, ULK4, FHIT, CD200, BTLA, TBL1XR1 | 3–21% | [66,67] |
14 | deletion of 14q | DPF3 | 3–21% | [58] |
7 | deletion of 7q deletion of 7p | IKZF1, IGF2BP | 3–18% | [2,58] |
4 | duplication of 4q deletion of 4q | NR3C2, YIPF7, ARHGAP10 | 6–17% | [66] |
19 | deletion of 19q | CEBPA, UHRF1, GRLF1, NPAS1, TMEM160 | 6–13% | [67] |
X | monosomy X in females/ gain of X in males gain of Xp duplication of Xq | SPANXB, HMGB3, FAM50A, HTATSF1 | 4–11% | [66] |
11 | deletion of 11q deletion of 11p | CD44, RAG1/2, BACL2, GNG3, HNRPUL2, TTC9C, ATM, KMT2A, HRAS | 10% | [67,68] |
1 | deletion of 1q | TROVE2, GLRX2, CDC73, B3GALT2, PDE4B, NRAS, | 10% | [69] |
15 | deletion of 15q | LTK, MIRN626 | 10% | [70] |
13 | deletion of 13q/monosomy | BTG1, RB1, SERP2, DLEU1/2/7, STBP4, TRIM3, KCNRG, MIRN16-1, MIRN15A | 5–10% | [58] |
8 | deletion of 8p | CTSB, LOXL2, NKX3-1, WHSC1L1,FGFR1, IDO1, IDO2, KAT6A | 6–8% | [58,68] |
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Kaczmarska, A.; Derebas, J.; Pinkosz, M.; Niedźwiecki, M.; Lejman, M. The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21). Cells 2023, 12, 357. https://doi.org/10.3390/cells12030357
Kaczmarska A, Derebas J, Pinkosz M, Niedźwiecki M, Lejman M. The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21). Cells. 2023; 12(3):357. https://doi.org/10.3390/cells12030357
Chicago/Turabian StyleKaczmarska, Agnieszka, Justyna Derebas, Michalina Pinkosz, Maciej Niedźwiecki, and Monika Lejman. 2023. "The Landscape of Secondary Genetic Rearrangements in Pediatric Patients with B-Cell Acute Lymphoblastic Leukemia with t(12;21)" Cells 12, no. 3: 357. https://doi.org/10.3390/cells12030357