Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing
Abstract
:1. Introduction
2. Molecular Characterization of Myeloproliferative Neoplasms
2.1. Chronic Myeloid Leukemia, BCR-ABL1 Positive
2.1.1. Tyrosine Kinase Inhibitors (TKIs) and Transcript Levels
2.1.2. ABL1 Kinase Domain Mutations
2.1.3. Disease Diagnosis and Laboratory Monitoring
2.2. Philadelphia Chromosome-Negative Myeloproliferative Neoplasms (Ph- MPN)
2.2.1. Polycythemia Vera
2.2.2. Essential Thrombocythemia
2.2.3. Primary Myelofibrosis
2.3. Driver Mutations in Ph- MPNs
2.3.1. JAK2 Mutations
2.3.2. CALR Mutations
2.3.3. MPL Mutations
3. Molecular Diagnostics for Ph- MPNs
3.1. Detection of Driver Mutations
3.2. Detection of Somatic/Acquired Non-driver Mutations or “Cooperating Mutations”
4. Chronic Neutrophilic Leukemia and CSF3R Mutations
5. Chronic Eosinophilic Leukemia
6. Summary and Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Diagnosis | ||||||
---|---|---|---|---|---|---|
CML | PV | ET | PMF | CNL | ||
Gene | BCR-ABL1 | 100% | - | - | - | - |
JAK2V617F | - | >95% | 50–60% | 50–60% | - | |
JAK2 exon 12 | - | 3–4% | - | - | - | |
CALR | - | - | 25% | 20–24% | - | |
MPL | - | - | 1–4% | 8–10% | - | |
CSFR3 | - | - | - | - | 80–90% |
Gene | Function | Prognostic Implication |
---|---|---|
ASXL1 | Histone modification (Chromatin binding protein) | Also identified in age-related clonal hematopoiesis, CML and MPNs—associated with unfavorable prognosis and rapid progression to AML |
20q11 | ||
EZH2 | Histone modification (loss of function of H3K27 methyltransferase) | Implicated in Post-ET and Post-PV MF, unfavorable prognosis in PMF |
7q35-36 | ||
DNMT3A | DNA methylation (DNA methylase) | Somatic mutations identified in age-related clonal hematopoiesis, CML and MPNs—associated with rapid disease progression |
2p23 | ||
IDH1/2 | DNA methylation (converts isocitrate to α-ketoglutarate) | Implicated in disease progression |
2q33.3/15q26.1 | ||
TET2 | DNA methylation (essential in myelopoiesis) | Somatic mutations identified in age-related clonal hematopoiesis, CML and MPNs—associated with rapid disease progression |
4q24 | ||
SRSF2 | RNA splicing/spliceosome assembly | Associated with progression to Myelofibrosis, downregulates EZH2, unfavorable prognosis in PMF |
12q25.1 | ||
SF3B1 | RNA splicing/spliceosome assembly | Associated with the presence of ringed sideroblasts, increased incidence of anemia |
2q33.1 | ||
U2AF1 | RNA splicing/spliceosome assembly | Associated with disease progression to AML, unfavorable prognosis in PMF |
21q22.3 | ||
LNK | Negative regulator of JAK2 | Implicated in disease progression, also found in familial cases of erythrocytosis |
12q24 | ||
TP53 | Transcription factor (involved in cell cycle regulation, DNA repair and apoptosis) | TP53 associated with poor prognosis, also associated with disease progression to AML (in <3% cases) |
17p13.1 | ||
ETV6 | Transcription factor | Also associated with disease progression to AML (in <3% cases) |
12p13 | ||
RUNX1 | Transcription factor (hematopoiesis) | Also associated with disease progression to AML (in <3% cases), also seen in secondary AML (about 30% cases) |
21q22.3 | ||
CBL | Cytokine receptor in signal transduction pathways | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
11q23.3 | ||
FLT3 | Cytokine receptor in signal transduction pathways | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
13q12 | ||
NRAS | MAPK signaling pathway | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
1p13.2 | ||
NF1 | MAPK signaling pathway | Implicated in AML progression (rare in PMF, but found in 10–15% secondary AML) |
17q11 |
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Easwar, A.; Siddon, A.J. Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing. Life 2021, 11, 1158. https://doi.org/10.3390/life11111158
Easwar A, Siddon AJ. Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing. Life. 2021; 11(11):1158. https://doi.org/10.3390/life11111158
Chicago/Turabian StyleEaswar, Arti, and Alexa J. Siddon. 2021. "Genetic Landscape of Myeloproliferative Neoplasms with an Emphasis on Molecular Diagnostic Laboratory Testing" Life 11, no. 11: 1158. https://doi.org/10.3390/life11111158