Genetic abnormalities, clinical presentations, and targeted therapy of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions
| TK gene . | Most common fusion . | Partner genes/variants . | Typical clinical and BM manifestations . | Targeted therapy . |
|---|---|---|---|---|
| PDGFRA | Cryptic deletion at 4q12/ FIP1L1::PDGFRA | CDK5RAP2; STRN; KIF5B; TNKS2; ETV6, BCR | Common: CEL-like BM with frequent extramedullary involvement | Excellent response to TKI |
| Others: B-ALL/LL, AML or mast cell proliferations | ||||
| PDGFRB | t(5;12)(q32;p13.2)/ ETV6::PDGFRB | >30 partners, cryptic | Common: CEL-like or monocytosis with eosinophilia | Excellent response to TKI |
| Others: ALL/LL, AML or mast cell proliferations | ||||
| FGFR1 | t(8;13)(p11.2;q12.1)/ ZMYM2::FGFR1 | 15 other partners including BCR | Common: Extramedullary T-ALL/LL with BM MPN-like or blast phase of MPN; | High rate of response to FGFR inhibitor such as pemigatinib, especially for cases in chronic phase |
| Others: B-ALL/LL, myeloid sarcoma, AML or MPAL | ||||
| JAK2 | t(8;9)(p22;p24.1)/ PCM1::JAK2 | ETV6 and BCR | Common: MPN or MDS/MPN-like BM with eosinophilia | Limited responses to ruxolitinib |
| Others: B- and T-ALL/LL with BM MPN | ||||
| FLT3 | t(12;13)(p13.2;q12.2)/ ETV6::FLT3 | ZMYM2, TRIP11, SPTBN1, GOLGB1, CCDC88C, MYO18A, BCR | T-ALL/LL or myeloid sarcoma with CEL-like or MDS/MPN BM features | Various responses to specific FLT3 inhibitors |
| ETV6::ABL1 | t(9;12)(q34.1;p13.2)/ ETV6::ABL1 | Unknown | CML-like with frequent eosinophilia in chronic or blast phase | Various responses to second generation TKI |
| TK gene . | Most common fusion . | Partner genes/variants . | Typical clinical and BM manifestations . | Targeted therapy . |
|---|---|---|---|---|
| PDGFRA | Cryptic deletion at 4q12/ FIP1L1::PDGFRA | CDK5RAP2; STRN; KIF5B; TNKS2; ETV6, BCR | Common: CEL-like BM with frequent extramedullary involvement | Excellent response to TKI |
| Others: B-ALL/LL, AML or mast cell proliferations | ||||
| PDGFRB | t(5;12)(q32;p13.2)/ ETV6::PDGFRB | >30 partners, cryptic | Common: CEL-like or monocytosis with eosinophilia | Excellent response to TKI |
| Others: ALL/LL, AML or mast cell proliferations | ||||
| FGFR1 | t(8;13)(p11.2;q12.1)/ ZMYM2::FGFR1 | 15 other partners including BCR | Common: Extramedullary T-ALL/LL with BM MPN-like or blast phase of MPN; | High rate of response to FGFR inhibitor such as pemigatinib, especially for cases in chronic phase |
| Others: B-ALL/LL, myeloid sarcoma, AML or MPAL | ||||
| JAK2 | t(8;9)(p22;p24.1)/ PCM1::JAK2 | ETV6 and BCR | Common: MPN or MDS/MPN-like BM with eosinophilia | Limited responses to ruxolitinib |
| Others: B- and T-ALL/LL with BM MPN | ||||
| FLT3 | t(12;13)(p13.2;q12.2)/ ETV6::FLT3 | ZMYM2, TRIP11, SPTBN1, GOLGB1, CCDC88C, MYO18A, BCR | T-ALL/LL or myeloid sarcoma with CEL-like or MDS/MPN BM features | Various responses to specific FLT3 inhibitors |
| ETV6::ABL1 | t(9;12)(q34.1;p13.2)/ ETV6::ABL1 | Unknown | CML-like with frequent eosinophilia in chronic or blast phase | Various responses to second generation TKI |