t(3;11) translocation in treatment-related acute myeloid leukemia fuses MLL with the GMPS (GUANOSINE 5' MONOPHOSPHATE SYNTHETASE) gene.
The partner gene of MLL was identified in a patient with treatment-related acute myeloid leukemia in which the karyotype suggested t(3;11)(q25;q23). Prior therapy included the DNA topoisomerase II inhibitors, teniposide and doxorubicin. Southern blot analysis indicated that the MLL gene was involved in the translocation. cDNA panhandle polymerase chain reaction (PCR) was used, which does not require partner gene-specific primers, to identify the chimeric transcript. Reverse-transcription of first-strand cDNAs with oligonucleotides containing known MLL sequence at the 5' ends and random hexamers at the 3' ends generated templates with an intra-strand loop for PCR. In-frame fusions of either MLL exon 7 or exon 8 with the GMPS (GUANOSINE 5'-MONOPHOSPHATE SYNTHETASE) gene from chromosome band 3q24 were detected. The fusion transcript was alternatively spliced. Guanosine monophosphate synthetase is essential for de novo purine synthesis. GMPS is the first partner gene of MLL on chromosome 3q and the first gene of this type in leukemia-associated translocations. (Blood. 2000;96:4360-4362)
Pegram
L D
LD
Division of Oncology, Joseph Stokes Jr Research Institute, The Children's Hospital of Philadelphia, Pennsylvania 19104-4318, USA.
Megonigal
M D
MD
Lange
B J
BJ
Nowell
P C
PC
Rowley
J D
JD
Rappaport
E F
EF
Felix
C A
CA
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000648:ultrastructure; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics* / Q000648:ultrastructure; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018076:DNA, Complementary / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D017809:Fatal Outcome; D006801:Humans; D015479:Leukemia, Myelomonocytic, Acute / Q000209:etiology / Q000235:genetics*; D007953:Leukemia, Radiation-Induced / Q000209:etiology / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein; D009364:Neoplasm Recurrence, Local; D016609:Neoplasms, Second Primary / Q000209:etiology / Q000235:genetics*; D009447:Neuroblastoma / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D013713:Teniposide / Q000008:administration & dosage / Q000009:adverse effects; D014178:Translocation, Genetic / Q000235:genetics*; D019172:Transplantation Conditioning / Q000009:adverse effects; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects; D014916:Whole-Body Irradiation / Q000009:adverse effects
D018076:DNA, Complementary; D004273:DNA, Neoplasm; C418134:MLL-GMPS fusion protein, human; D015514:Oncogene Proteins, Fusion; D051788:Myeloid-Lymphoid Leukemia Protein; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D013713:Teniposide