IL-2-inducible T-cell kinase deficiency: clinical presentation and therapeutic approach.
Mutations in the IL-2-inducible T-cell kinase gene have recently been shown to cause an autosomal recessive fatal Epstein Barr virus (EBV) associated lymphoproliferation. We report 3 cases from a single family who presented with EBV-positive B-cell proliferation diagnosed as Hodgkin's lymphoma. Single nucleotide polymorphism array-based genome-wide linkage analysis revealed IL-2-inducible T-cell kinase as a candidate gene for this disorder. All 3 patients harbored the same novel homozygous nonsense mutation C1764G which causes a premature stop-codon in the kinase domain. All cases were initially treated with chemotherapy. One patient remains in durable remission, the second patient subsequently developed severe hemophagocytic lymphohistiocytosis with multi-organ failure and died, and the third patient underwent a successful allogeneic bone marrow transplantation. IL-2-inducible T-cell kinase deficiency underlies a new primary immune deficiency which may account for part of the spectrum of Epstein Barr virus related lymphoproliferative disorders which can be successfully corrected by bone marrow transplantation.
Pediatric Hematology-Oncology, Hadassah Hebrew University Medical Center, PO Box 12000, Jerusalem 91120, Israel. polina@hadassah.org.il
Polina
P
Stepensky
Michael
M
Weintraub
Asaf
A
Yanir
Shoshana
S
Revel-Vilk
Frank
F
Krux
Kirsten
K
Huck
Rene M
RM
Linka
Avraham
A
Shaag
Orly
O
Elpeleg
Arndt
A
Borkhardt
Igor B
IB
Resnick
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002675:Child, Preschool; D018389:Codon, Nonsense; D003643:Death; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy; D005260:Female; D004854:Herpesvirus 4, Human / Q000254:growth & development; D006689:Hodgkin Disease / Q000209:etiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006720:Homozygote; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051359:Lymphohistiocytosis, Hemophagocytic / Q000401:mortality / Q000473:pathology; D008297:Male; D010375:Pedigree; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000276:immunology; D012074:Remission Induction; D014184:Transplantation, Homologous / Q000276:immunology*
D000970:Antineoplastic Agents; D018389:Codon, Nonsense; D011505:Protein-Tyrosine Kinases; C080813:emt protein-tyrosine kinase