Table 1. Gene abnormalities and cytogenetic defects in myeloid and stem cell neoplasms associated with eosinophilia.
| Molecular defect fusion gene/mutation | Cytogenetic anomaly | Estimated frequency in MPN-eo (%) |
Estimated frequency in CEL (%) |
|---|---|---|---|
| PDGFRA gene abnormalities | |||
| FIP1L1-PDGFRA | del(4q12) | 5 | 10–20 |
| STRN-PDGFRA | t(2;4)(p22;q12) | <5 | <5 |
| CDK5RAP2-PDGFRA | ins(9;4)(q33;q12;q25) | <5 | <5 |
| KIF5B-PDGFRA | t(4;10)(q12;p11) | <5 | <5 |
| BCR-PDGFRA | t(4;22)(q12;q11) | <5 | <5 |
| ETV6-PDGFRA | t(4;12)(q12;p13) | <5 | 5 |
| PDGFRB gene abnormalities | |||
| TPM3-PDGFRB | t(1;5)(q21;q33) | <1 | <1 |
| PDE4DIP-PDGFRB | t(1;5)(q23;q33) | <1 | <1 |
| SPTBN1-PDGFRB | t(2;5)(p16;q33) | <1 | <1 |
| WDR48-PDGFRB | t(3;5)(p22;q33) | <1 | <1 |
| GOLGA4-PDGFRB | t(3;5)(p22;q33) | <1 | <1 |
| PRKG2-PDGFRB | t(4;5;5)(q23;q23;q31) | <1 | <1 |
| HIP1-PDGFRB | t(5;7)(q33;q11) | <1 | <1 |
| KANK1-PDGFRB | t(5;9)(q33;p24) | <1 | <1 |
| CCDC6-PDGFRB | t(5;10)(q33;q21) | <1 | <1 |
| CAPRIN1-PDGFRB | t(1;5;11)(p34;q33;p13) | <1 | <1 |
| ERC1-PDGFRB | t(5;12)(q33;p13) | <1 | <1 |
| BIN2-PDGFRB | t(5;12)(q33;q13) | <1 | <1 |
| ETV6-PDGFRB | t(5;12)(q33;p13) | <1 | <1 |
| SART3-PDGFRB | t(5;12)(q33;q24) | <1 | <1 |
| GIT2-PDGFRB | t(5;12)(q33;q24) | <1 | <1 |
| CCDC88C-PDGFRB | t(5;14)(q33;q32) | <1 | <1 |
| TRIP11-PDGFRB | t(5;14)(q33;q32) | <1 | <1 |
| NIN-PDGFRB | t(5;14)(q33;q24) | <1 | <1 |
| TP53BP1-PDGFRB | t(5;15)(q33;q22) | <1 | <1 |
| NDE1-PDGFRB | t(5;16)(q33;p13) | <1 | <1 |
| SPECC1-PDGFRB | t(5;17)(q33;p11) | <1 | <1 |
| MYO18A-PDGFRB | t(5;17)(q33;q11) | <1 | <1 |
| RABEP1-PDGFRB | t(5;17)(q33;p13) | <1 | <1 |
| FGFR1 gene abnormalities | |||
| FGFR1OP-FGFR1 | t(6;8)(q27;p11) | <1 | <1 |
| TRIM24-FGFR1 | t(7;8)(q34;p11) | <1 | <1 |
| CEP110-FGFR1 | t(8;9)(p12;q33) | <1 | <1 |
| CPSF6-FGFR1 | t(8;12)(p11;q15) | <1 | <1 |
| FGFR1OP-FGFR1 | t(6;8)(q27;p11) | <1 | <1 |
| NUP98-FGFR1 | t(8;11)(p11;p15) | <1 | <1 |
| HERVK-FGFR1 | t(8;19)(p11;q13) | <1 | <1 |
| FGFR1OP2-PDGFRA | ins(12;8)(p11;p11p22) | <1 | <1 |
| ZMYM2-FGFR1 | t(8;13)(p11;q12) | <1 | <1 |
| MYO18A-FGFR1 | t(8;17)(p11;q23) | <1 | <1 |
| CUX1-FGFR1 | t(7;8)(q22;p11) | <1 | <1 |
| LRRFIP1-FGFR1 | t(2;8)(q37;p11) | <1 | <1 |
| BCR-FGFR1 | t(8;22)(p11;q11) | <1 | <1 |
| Abnormalities and mutations in other genes | |||
| PCM1-JAK2 | t(8;9)(p21;p24) | <1 | <1 |
| ETV6-JAK2 | t(9;12)(p24;p13) | <1 | <1 |
| BCR-JAK2 | t(9;22)(q11;p24) | <1 | <1 |
| SPTBN1-FLT3 | t(2;13)(p16;q12) | <1 | <1 |
| ETV6-FLT3 | t(12;13)(p13;q12) | <1 | <1 |
| ETV6-ACSL6 | t(5;12)(q33;p12) | <1 | <1 |
| CBF-MYH11 | inv(16) | <1 | <1 |
| BCR-ABL1 | t(9;22)(q34;q11) | <1 | <1 |
| KIT D816V | – | <1 | <1 |
| JAK2 V617F | – | <1 | <1 |
|
PDGFRA Y849S/ N659S |
– | <1 | <1 |
Molecular defects refer to data reported in the available literature. Histomorphologic phenotypes and variants reported in these patients include CEL, myeloproliferative syndromes with eosinophilia (MPN-eo), myelodysplastic syndromes with eosinophilia (MDS-eo), MPN/MDS overlap syndromes with eosinophilia (MPN/MDS-eo), chronic myelomonocytic leukemia with eosinophilia, chronic myeloid leukemia, atypical chronic myeloid leukemia with eosinophilia, systemic mastocytosis with eosinophilia, aggressive systemic mastocytosis with eosinophilia, acute myeloid leukemia with eosinophilia, acute eosinophilic leukemia and stem cell syndromes, including the stem cell leukemia lymphoma syndrome and the 8p11 syndrome. By far the most frequent fusion gene is FIP1L1-PDGFRA, which is found in 5–15% of all cases with nonreactive HE. Other more rarely but recurrently identified molecular abnormalities (>5 cases reported) include ZMYM2-FGFR1 (formerly known as ZNF198-FGFR1), FGFR1OP-FGFR1 (FOP-FGFR1), CEP110-FGFR1, PCM1-JAK2, ETV6-JAK2, KIT D816V, CCDC6-PDGFRB (H4/D10S170) and ETV6 PDGFRB (TEL-PDGFRB). The majority of PDGFRB fusion genes have only been reported in single individuals.
CEL: Chronic eosinophilic leukemia; MPN-eo: Myeloproliferative neoplasms with eosinophilia.