A deletion polymorphism in the RIZ gene is associated with increased progression of imatinib treated chronic myeloid leukemia patients.
RIZ1 encodes a retinoblastoma (Rb)-interacting zinc finger protein, is commonly lost or expressed at reduced levels in cancer cells. The RIZ1 gene locus commonly undergoes LOH in many cancers. Here, we analyzed Proline insertion-deletion polymorphism at amino acid position 704 in the RIZ1 gene and its association with CML. The RIZ1 pro-704 LOH genotypes were determined by AS-PCR in 100 CML patients among which 50 were in CP-CML, 25 in AP-CML, and 25 in BC-CML. Pro704 ins/del polymorphism (LOH) was detected in 27% CML patients. Proline ins-ins homozygosity, del-del homozygosity and ins-del heterozygosity was detected in 9%, 18%, and 73% CML patients compared with 3%, 3%, and 94% in healthy controls, respectively (p < .0003). A four-fold increased risk was found to be associated del-del genotype. We found a statistically significant association between RIZ1 LOH and stage (p > .01) and hematological resistance (p > .001). However, there were no correlations found with other clinical parameters like age, gender, thrombocytopia, type of BCR-ABL, and molecular response. Our findings suggest that proline 704 del-del homozygosity phenotype can play an important role in progression of CML.
a Prince Fahd Bin Sultan Research Chair, Cancer Molecular Genetics, Faculty of Applied Medical Sciences , University of Tabuk , Tabuk , Saudi Arabia.
Rashid
R
Mir
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Imtiyaz Ah
IA
Najar
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Sameer
S
Guru
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Jamsheed
J
Javaid
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Prasant
P
Yadav
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Mirza
M
Masroor
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Mariyam
M
Zuberi
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Shazia
S
Farooq
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Musadiq
M
Bhat
c Department of Medicine , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Naresh
N
Gupta
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Prakash Chander
PC
Ray
b Department of Biochemistry , Maulana Azad Medical College and Associated Hospitals , New Delhi , India.
Alpana
A
Saxena
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics; D005838:Genotype; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D054643:INDEL Mutation; D000068877:Imatinib Mesylate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic; D016896:Treatment Outcome
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D000068877:Imatinib Mesylate; D011495:Histone-Lysine N-Methyltransferase; C093563:PRDM2 protein, human; D016044:Fusion Proteins, bcr-abl
Basic biology; drug resistance; genetic and other predisposing conditions