Transcript-Level Dysregulation of BCL2 Family Genes in Acute Myeloblastic Leukemia
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
3. Results
3.1. Expression of Genes Encoding Proteins from the BCL2 Family
3.2. Expression of the BCL2L1 Gene Isoforms
3.3. Expression of Genes Encoding Proteins Interacting with BCL2L1
3.4. Impact of the BCL2 Gene Family Expression Levels on the Patient Outcome
3.5. Mutation Analysis of the BCL2 Family Genes and Genes Encoding Proteins Interacting with BCL2L1
3.6. Mutation Analysis in the Genes Encoding Splicing-Associated Proteins
3.7. Relations between the BCL2 Family Gene Expression, Mutation Status, and Other Clinical Features
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Group | Number of Patients (F/M) | FAB Type (Number) | Age Median (Range) | WBC Count [×109/L] Mean (Range) | NPM1 mut. | FLT3 mut. | RUNX1/RUNX1T1 | Karyotype |
---|---|---|---|---|---|---|---|---|
CR | 11 (6/5) | M1 (3) M2 (8) | 52 (19–64) | 36.3 (3.6–111) | 2 | 2 | 2 | normal (1) aberrant (4) NA (6) |
RES | 8 (3/5) | M1 (2) M2 (6) | 53.5 (21–64) | 62.17 (1.3–146) | 2 | 1 | 1 | normal (1) aberrant (4) NA (3) |
X | 8 (4/4) | M1 (4) M2 (4) | 51 (25–65) | 90.43 (19.9–233) | 3 | 1 | - | normal (1) aberrant (2) NA (5) |
All patients | 27 (13/14) | M1 (9) M2 (18) | 52 (19–65) | 60.0 (1.3–233) | 7 | 4 | 3 | normal (3) aberrant (10) NA (14) |
Group | BCL2A1/BCL2L1 Ratio | BCL2/BCL2L11 Ratio |
---|---|---|
AML—mean ratio (st. dev.) CR—mean ratio (st. dev.) RES—mean ratio (st. dev.) | 1.15 (1.02) | 3.26 (2.53) |
1.31 (0.7) | 2.93 (2.43) | |
0.92 (1.44) | 3.16 (3.05) | |
X—mean ratio (st. dev.) ctrl—mean ratio (st. dev.) | 1.15 (0.99) | 3.81 (2.3) |
5.67 (4.56) | 0.83 (0.50) | |
AML vs. ctrl * CR vs. ctrl* | 0.0034 | 0.033 |
0.0110 | 0.1264 | |
RES vs. ctrl * X vs. ctrl * | 0.0485 | 0.1333 |
0.0121 | 0.0121 | |
RES vs. X * | 0.5054 | 0.3823 |
RES vs. CR * | 0.0506 | 0.9678 |
CR vs. X * | 0.5448 | 0.3950 |
BCL2L1 Gene Isoform | Length of the Gene (Protein) | CR—Mean TPM (st. dev.) | RES—Mean TPM (st. dev.) | X—Mean TPM (st. dev.) | Ctrl—Mean TPM (st. dev.) |
---|---|---|---|---|---|
ENST00000307677 | 2574 bp (233 aa) | 39.14 (32.37) | 101.71 (140.27) | 48.01 (56.36) | 14.90 (4.68) |
ENST00000376055 | 2496 bp (170 aa) | 7.05 (8.13) | 26.29 (50.13) | 6.89 (7.52) | 6.32 (5.18) |
ENST00000376062 | 2578 bp (233 aa) | 4.49 (3.26) | 5.55 (5.80) | 4.67 (4.93) | 3.39 (2.95) |
ENST00000420488 | 2444 bp (233 aa) | 0.41 (0.45) | 0.75 (0.88) | 0.22 (0.26) | 0.11 (0.19) |
ENST00000422920 | 2227 bp (170 aa) | 1.82 (0.91) | 5.89 (8.84) | 2.44 (2.62) | 0.97 (0.15) |
ENST00000434194 | 2441 bp (233 aa) | 0.10 (0.25) | 0.11 (0.19) | 0.23 (0.45) | 0.16 (0.28) |
ENST00000439267 | 2426 bp (233 aa) | 0.48 (0.53) | 0.48 (0.51) | 0.63 (0.67) | 0.25 (0.22) |
ENST00000450273 | 1292 bp (307 aa) | 0.35 (0.50) | 0.51 (0.52) | 0.48 (0.59) | 0.76 (0.40) |
ENST00000456404 | 2562 bp (233 aa) | 0.97 (0.63) | 0.72 (0.83) | 1.20 (0.95) | 0.87 (0.47) |
Expression of Genes | Associated Factor | p Value |
---|---|---|
BCL2L1, BID, BOK, HRK | BRCA2_status, RUNX1_status | 4.145 × 10−10 *** 0.04287 * |
BCL2L1, BID, BOK, HRK | BRCA2 status | 2.106 × 10−9 *** |
BCL2L1, BID, HRK | RUNX1 status | 0.0002187 *** |
BCL2L10, BCL2L2, HRK | HNRNPU status | 8.038 × 10−7 *** |
BCL2L1, BBC3, BOK, BCL2L10, BCL2L11 | HNRNPH2 status | 1.129 × 10−5 *** |
BCL2L11, BCL2L13, BID, BIK, BNIP1 | WBC count | 6.459 × 10−5 *** |
HRK, BAK1, BCL2A1, BID, BNIP1 | SNRNP200 status | 0.002168 ** |
BCL2L10, BNIP2 | DDX42 status | 0.000545 *** |
BCL2, BCL2A1, BCL2L10, BID, BNIP1, MCL1 | CWC27 status | 0.007744 ** |
BMF, RTL10, BAX, BCL2L11, BCL2L2 | CEBPA status | 0.00383 ** |
BCL2L13, BIK, PMAIP1 | RBMX status | 0.0004931 *** |
MCL1, BCL2L11 | HNRNPUL1 status | 0.05703 |
BCL2L2.PABPN1, BNIP2 | DHX38 status | 0.009772 ** |
BCL2, BCL2L11, BCL2L12, BCL2L15 | EP300 status | 0.04793 * |
BCL2L13, BCL2L2, BIK | ATM status | 0.003997 ** |
BAX, BCL2A1, BNIP2 | KRAS status | 0.01254 * |
BCL2L13, BCL2L2 | DNMT3A status | 0.02401 * |
BNIP1, BCL2L2.PABPN1 | IDH1 status | 0.01978 * |
BBC3, BCL2L1, BCL2L11, BOK, MCL1 | IDH2 status | 0.02641 * |
BCL2L1, BOK | IDH2 status, MCL1 status | 0.001286 ** 0.007325 ** |
BCL2L1, BOK | IDH2 status, MCL1 status, BRCA2 status | 1.755 × 10−5 *** 4.508 × 10−5 *** 4.624 × 10−6 *** |
BCL2L1, BOK | MCL1 status | 0.001242 ** |
BAD, BAK1, BCL2L11, BID, BNIP2, BNIP3 | RUNX1-RUNX1T1 status | 0.002101 ** |
BCL2L13, BID, BIK, BNIP1 | NPM1 status | 0.02555 * |
BAD, BAX, BCL2L1, BCL2L11, BCL2L13, BCL2L2.PABPN1, BID, BIK, BNIP1, BOK | Blast percentage in PB | 0.003099 ** |
BCL2L1, BCL2L11, BCL2L15, BCL2L2.PABPN1, BID, BIK, BNIP1, BOK, HRK | Blast percentage in BM | 0.000261 *** |
BAK1, BBC3, BCL2L1, BCL2L11, BCL2L12, BOK | Tissue type (PB, BM) | 0.0004833 *** |
BCL2L15, BCL2L2, BNIP1, BNIP3 | FAB type (M1, M2) | 0.03326 * |
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Handschuh, L.; Wojciechowski, P.; Kazmierczak, M.; Lewandowski, K. Transcript-Level Dysregulation of BCL2 Family Genes in Acute Myeloblastic Leukemia. Cancers 2021, 13, 3175. https://doi.org/10.3390/cancers13133175
Handschuh L, Wojciechowski P, Kazmierczak M, Lewandowski K. Transcript-Level Dysregulation of BCL2 Family Genes in Acute Myeloblastic Leukemia. Cancers. 2021; 13(13):3175. https://doi.org/10.3390/cancers13133175
Chicago/Turabian StyleHandschuh, Luiza, Pawel Wojciechowski, Maciej Kazmierczak, and Krzysztof Lewandowski. 2021. "Transcript-Level Dysregulation of BCL2 Family Genes in Acute Myeloblastic Leukemia" Cancers 13, no. 13: 3175. https://doi.org/10.3390/cancers13133175