Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia-associated myeloproliferative neoplasms.
In eosinophilia-associated myeloproliferative neoplasms (MPN-eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN-eo patients: MPRIP-PDGFRB in a case with t(5;17)(q33;p11), CPSF6-PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1-PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5'-rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA-based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled-coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions.
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Nicole
N
Naumann
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Juliana
J
Schwaab
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Georgia
G
Metzgeroth
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Mohamad
M
Jawhar
MLL Münchner Leukämielabor GmbH, München, Germany.
Claudia
C
Haferlach
Institut Für Humangenetik, Medizinische Hochschule Hannover, Hannover, Germany.
Gudrun
G
Göhring
Institut Für Humangenetik, Medizinische Hochschule Hannover, Hannover, Germany.
Brigitte
B
Schlegelberger
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Christian T
CT
Dietz
MLL Münchner Leukämielabor GmbH, München, Germany.
Susanne
S
Schnittger
Onkologie MVZ Am Siloah St. Trudpert Klinikum Pforzheim, Pforzheim, Germany.
Sina
S
Lotfi
Onkologisches Ambulanzzentrum Hannover, Hannover, Germany.
Michael
M
Gärtner
Medizinische Klinik V, Klinikum Darmstadt, Darmstadt, Germany.
Tu-Anh
TA
Dang
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Wolf-Karsten
WK
Hofmann
Wessex Regional Genetics Laboratory, Salisbury, UK.|Faculty of Medicine, University of Southampton, UK.
Nicholas C P
NC
Cross
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Andreas
A
Reiter
III. Medizinische Klinik, Universitätsmedizin Mannheim, Mannheim, Germany.
Alice
A
Fabarius
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D020732:Cytogenetic Analysis; D004802:Eosinophilia / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D050939:Gene Fusion; D000077614:Golgi Matrix Proteins; D006801:Humans; D000068877:Imatinib Mesylate / Q000627:therapeutic use; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics*; D012074:Remission Induction; D014178:Translocation, Genetic; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics*
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D000077614:Golgi Matrix Proteins; C498552:MPRIP protein, human; D008565:Membrane Proteins; C450562:cleavage factor Im, human; D039221:mRNA Cleavage and Polyadenylation Factors; C087574:macrogolgin; D000068877:Imatinib Mesylate; C000605860:PDGFRB protein, human; D020797:Receptor, Platelet-Derived Growth Factor beta