World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website http://www.wjon.org

Original Article

Volume 6, Number 2, April 2015, pages 321-328

Polymorphism T81C in H-RAS Oncogene Is Associated With Disease Progression in Imatinib (TKI) Treated Chronic Myeloid Leukemia Patients

Figures

Figure 1.
Figure 1. Ethidium bromide stained agarose gel electrophoresis image of H-RAS T81C polymorphism.
Figure 2.
Figure 2. Association of H-RAS T81C with stages of CML.
Figure 3.
Figure 3. Frequency of TT genotype of T81C H-RAS in different cancers.
Figure 4.
Figure 4. Frequency of CT genotype of T81C H-RAS in different cancers.

Tables

Table 1. Hematologic Responses
 
Complete or major hematological responsePartial or minor hematological responseLose or minimal hematological response
Platelet count >150 × 109/L
WBC count < 10 × 109/L
Basophils: < 5%
Differential without immature granulocytes
Absence of blasts and promyelocytes in peripheral blood
Spleen: non-palpable spleen		Platelet count < 450 × 109/L
WBC count > 10 × 109/L
Basophils: > 10%
Presence of blasts and promyelocytes in peripheral blood
Spleen: palpable spleen		Platelet count < 450 × 109/L
WBC count > 20 × 109/L
Basophils: 15%
Presence of blasts and promyelocytes in peripheral blood
Spleen: palpable spleen

 

Table 2. Molecular Response
 
Major molecular responseMinimal or no molecular response
*BCR-ABL to control gene ratio according to international scale (IS).
It indicates non-quantifiable and non-detectable BCR-ABL gene transcript (BCR-ABL/ABL) ≤ 0.103*
check every 3 months		It indicates quantifiable and detectable BCR-ABL gene transcript (BCR-ABL/ABL) ≥ 0.103*
check every 3 months

 

Table 3. Sequence of Oligonucleotides Used in Multiplex RT-PCR for Detection of BCR-ABL Transcript as the Target Gene and BCR Transcripts as the Internal Control
 
BCR-ABL primers
C5e 5'-ATAGGATCCTTTGCAACCGGGTCTGAA-3'
B2B 5'-ACAGAATTCCGCTGACCATCAATAAG-3'
BCR-C 5'-ACCGCATGTTCCGGGACAAAAG-3'
CA3 5'-TGTTGACTGGCGTGATGTAGTTGCTTGG-3'

 

Table 4. Sequence of Oligonucleotides Used in Allele Specific PCR of H-RAS Gene
 
GeneH-RAS
Forward primer5'-CTTGGCAGGTGGGGCAGGAGA-3'
Reverse primer5'-GGCACCTGGACGGCGGCGCTAG-3'

 

Table 5. Clinical-Pathological Parameters of CML Patients
 
No.%
Patients100100%
controls100100%
Males6565%
Female3535%
CP-CML5050%
AP-CML2525%
BC-CML2525%
Imatinib100100%
MMR5252%
No MR4848%
MHR5050%
Minor HR1010%
Loss HR4040%
Age > 453636%
Age < 456464%
Thrombocytopenia5050%
No thrombocytopenia5050%

 

Table 6. Association of H-RAS T81C Polymorphism With the Clinicopathological Features
 
Clinical featuresNo.TTCTCCP value
Patients10038611< 0.0001
Controls1009280
Males6525391< 0.7
Female3513220
CP-CML5029201< 0.0003
AP-CML257180
BC-CML252230
A2b23113180< 0.9
A2b36724421
A2b2/A2b32110
Imatinib10038611
MMR5231210< 0.0001
No MR487401
MHR5026240< 0.04
Minor HR10370
Loss HR409301
Age > 453611241< 0.2
Age ≤ 456427370
Thrombocytopenia5011381< 0.003
No thrombocytopenia5027230

 

Table 7. Risk of CML Associated With the H-RAS Genotypes
 
GenotypingCases (n = 100)Control (100)OR* (95% CI)P value
OR: odds ratio.
TT38 (38%)92(92%)1
TC61 (61%)8 (8%)18.4 (8.0-14.2)< 0.0001
CC1 (61%)0 (0%)-
Allele type
  T allele136(68.6%)184(95.8%)1
  C allele62 (32.2%)8 (4.1%)10.4 (4.8-22.6)< 0.0001

 

Table 8. Frequency of T81C Genotypes in Different Cancers
 
Cancer typeTT genotypeCT genotypeCC genotypeReferences
Rectal cancer75.2%24.7%0%16
Colon cancer76.3%21.5%2.1%16
Gastric cancer79.24%19.87%0.89%16
Thyroid cancer37.6%44.7%17.7%29
Urinary bladder cancer48.3%38.1%13.4%34
Colon cancer60.5%36.5%3%35
Oral cancer53.7%39.4%6%36
Urinary bladder cancer34.1%48.5%17.4%37