Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options
Abstract
:1. Introduction
2. Clinical Risk Factors
3. Biological Risk Factors
4. Morphological and Histological Characteristics of MPN Progression
5. Karyotype
6. Molecular Profile
7. Therapy
8. Supportive Therapy
9. Hypomethylating Agents
9.1. Azacitidine
9.2. Decitabine
10. Other Therapies
11. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Gene | Gene Function | Chromosome Location | Prognostic Significance | References |
---|---|---|---|---|
ASXL1 | Epigenetic regulation | 20q11.1 | Adverse in PV and PMF | [28,29,30] |
SRSF2 | mRNA processing | 17q25.1 | Adverse in PV, ET and PMF | [28,30] |
EZH2 | Epigenetic regulation | 7q36.1 | Adverse in ET and PMF | [28,30] |
IDH1 | Epigenetic regulation | 2q33.3 | Adverse in PMF | [28,30,31,32] |
IDH2 | Epigenetic regulation | 15q26.1 | Adverse in PV, ET and PMF | [28,30,31,32] |
CBL | Cell signaling pathways | 11q23.3 | Adverse in PMF | [30] |
RUNX1 | Transcriptional regulation | 21q22.12 | Adverse in PV and PMF | [30] |
CEBPA | Transcriptional regulation | 19q13.1 | Adverse in PMF | [30] |
SH2B3 | mRNA processing | 12q24 | Adverse in ET and PMF | [30] |
KIT | Tyrosine kinase receptor | 4q11 | Adverse in PMF | [30] |
TP53 | Transcriptional regulation | 17p13.1 | Adverse in ET | [33] |
Treatment Approach | Patient Population | Results | Survival | References |
---|---|---|---|---|
HMAs | MPN-BP (n = 26); MPN-AP (n = 28) | ORR, 52% with azacitidine | 11 months | [52] |
MPN-BP (n = 19) | ORR, 47% with azacitidine | 9.9 months | [53] | |
MPN-BP (n = 21); MPN-AP (n = 13); PMF (n = 11) | ORR in MPN-BP, 29% with decitabine | 6.9 months | [54] | |
JAK inhibition | R/R AML (n = 38), including MPN-BP (n = 18) | CR/CRi 17% | NR | [55] |
R/R AML (n = 28), including MPN-BP (n = 7) | ORR, 0% | NR | [56] | |
JAK inhibition + HMAs | MPN-BP/AP (n = 21) | ORR; 33% | 10.4 months | [57] |
MPN-BP (n = 10) | ongoing | NR | [58] |
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Iurlo, A.; Cattaneo, D.; Gianelli, U. Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options. Int. J. Mol. Sci. 2019, 20, 1839. https://doi.org/10.3390/ijms20081839
Iurlo A, Cattaneo D, Gianelli U. Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options. International Journal of Molecular Sciences. 2019; 20(8):1839. https://doi.org/10.3390/ijms20081839
Chicago/Turabian StyleIurlo, Alessandra, Daniele Cattaneo, and Umberto Gianelli. 2019. "Blast Transformation in Myeloproliferative Neoplasms: Risk Factors, Biological Findings, and Targeted Therapeutic Options" International Journal of Molecular Sciences 20, no. 8: 1839. https://doi.org/10.3390/ijms20081839