Chronic myeloproliferative disorders: a tyrosine kinase tale

K De Keersmaecker and J Cools


Table 1. Overview of the chromosomal aberrations and mutations involving tyrosine kinase genes in CMPD

Chromosomal abnormality Oncogene Targeted therapy CMPD entity
 9q34ABL1Imatinib,42 AMN-107,43 BMS-35482544  
t(9;22)(q34;q11)BCR-ABL11  CML
t(9;12)(q34;p13) ETV6-ABL1 45  CML-like
 5q33PDGFRBImatinib,46 AMN-10747 CEL (CMML)
t(5;12)(q33;p13) ETV6-PDGFRB 48   
t(5;7)(q33;q11) HIP1-PDGFRB 49   
t(5;10)(q33;q21) CCDC6-PDGFRB 50, 51   
t(5;14)(q33;q32) KIAA1509-PDGFRB 52   
t(5;14)(q33;q32) TRIP11-PDGFRB 53   
t(5;14)(q33;q22) NIN-PDGFRB 54   
t(5;15)(q33;q15) TP53BP1-PDGFRB 55   
t(5;17)(q33;p11) SPECC1-PDGFRB 56   
t(5;17)(q33;p13) RABEP1-PDGFRB 57   
 8p11 FGFR1 PKC41258 CEL
t(8;13)(p11;q12) ZNF198-FGFR1 59, 60, 61   
t(7;8)(q32;p11) TRIM24-FGFR1 62   
t(6;8)(q27;p11) FGFR1OP-FGFR1 63   
ins(12;8)(p11;p11p22) FGFR1OP2-FGFR1 64   
t(8;17)(p11;q11) MYO18A-FGFR1 65   
t(8;22)(p11;q11) BCR-FGFR1 66   
t(8;19)(p12;q13.3) LOC113386-FGFR1 67   
t(8;9)(p12;q33) CEP1-FGFR1 68   
 4q12 PDGFRA Imatinib,8 PKC412,22 AMN-10747 CEL
del(4)(q12q12) FIP1L1-PDGFRA 8   
t(4;22)(q12;q11) BCR-PDGFRA 14   
 4q12 KIT PKC412,30, 31 AMN-10732 SM
None KIT(D816V)   
None JAK2(V617F) het PV, ET, IM*
uniparental disomy JAK2(V617F) hom9, 10, 11, 12   
t(9;22)(p24;q11) BCR-JAK2 69  CML-like
t(8;9)(p22;p24) PCM1-JAK2 4, 5, 6  various
 NoneUnknownResponse to imatinib treatment without known cause of the disease8, 15, 17 CEL

 The HUGO gene symbol is provided for all genes; previous gene nomenclature: ABL1 (ABL), CEP1 (CEP110), ETV6 (TEL), CCDC6 (H4), TRIP11(CEV14), SPECC1(HCMOGT1), RABEP1(RABAPTIN5), TRIM24 (TIF1), LOC113386 (HERV-K). het, heterozygous mutation; hom, homozygous mutation. *The JAK2 mutation is most common in PV, ET and IM, but has now also been identified in other CMPDs, including some cases with CNL, CEL, and atypical CML.26, 27, 28