Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Reagents and Drugs
2.2. Pediatric Samples
2.3. Apoptosis Assay
2.4. Analysis of In Vivo Efficacy and Self-Renewal Capacity
2.5. Statistical Analysis
3. Results
3.1. Imetelstat Suppresses the Viability of Pediatric AML LSCs in PDX Samples Ex Vivo
3.2. Imetelstat Reduces the LSC Population In Vivo and Prolongs Survival in Two PDX Models
3.3. Imetelstat Delays Engraftment and Improves Survival in Secondary Transplantation Model
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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Sample | Ethnicity | Age (Years)/Sex | AML Sub Type | Sample Collected at | FISH | Karyotype | Genomics (Archer Panel) |
---|---|---|---|---|---|---|---|
NTPL-60 | African American | 4/M | M7 | Diagnosis | Trisomy 21, AML1 and ETO amplification | 46, XY der (14;21) (q10;q10), +21c [cp12]/48, idem, +8, +der (14;21) (q10; q10) [cp8}− | GATA1 mutation |
NTPL-377 | Hispanic | 1.5/F | M5 | Diagnosis | KMT2A rearrangement | 46, XX, t(9;11)(p21;q23)[20] | KMT2A-MLLT3 (56%) |
NTPL-386 | Non-Hispanic | 2/M | M7 | Diagnosis | Trisomy 21, RUNX1 amplification | 47,XY,del(13)(q12q14),+21c [12]/47,ldem,l(7)(q10)[3]/47,XY,+21c[5] | GATA1 mutation; KMT2A-TMEM25 (8%) |
NTPL-511 | Unknown | 14/M | M2 | Diagnosis | Negative | 47, XY,+8[1]/46,XY[29] | NUP98-NSD1 (20%); NSD1-NUP98 (7%) |
NTPL-662 | Unknown | 14/M | M7 | Diagnosis | Trisomy 21, low level trisomy 8 | 47, XY,+21c[91]/48,idem,+8[2] | none |
DF-2 (CBAM-68552) | Caucasian | 1/M | M5 | Relapse following chemotherapy | KMT2A rearrangement | 46,XY,inv(6)(q23q27)[20] | KMT2A-MLLT4 (54%) |
NTPL-257 | Caucasian | 3/F | Normal | ||||
NTPL-793 | Caucasian | 13/F | Normal | ||||
NTPL-827 | African American | 0.6/M | Normal | ||||
NTPL-837 | African American | 2/M | Normal |
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Barwe, S.P.; Huang, F.; Kolb, E.A.; Gopalakrishnapillai, A. Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts. J. Clin. Med. 2022, 11, 1923. https://doi.org/10.3390/jcm11071923
Barwe SP, Huang F, Kolb EA, Gopalakrishnapillai A. Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts. Journal of Clinical Medicine. 2022; 11(7):1923. https://doi.org/10.3390/jcm11071923
Chicago/Turabian StyleBarwe, Sonali P., Fei Huang, Edward Anders Kolb, and Anilkumar Gopalakrishnapillai. 2022. "Imetelstat Induces Leukemia Stem Cell Death in Pediatric Acute Myeloid Leukemia Patient-Derived Xenografts" Journal of Clinical Medicine 11, no. 7: 1923. https://doi.org/10.3390/jcm11071923