Prediction of IGHV Mutational Status Among Patients with Chronic Lymphocytic Leukemia

Background: IGHV mutational status is a crucial test in precision medicine and selecting a treatment strategy for patients with chronic lymphocytic leukemia (CLL). However, this test is not widely available across the GCC. Method: IGHV mutational status was tested in a cohort of 177 local CLL cohort at Kuwait Cancer Center. The results were tested in a logistic regression model in cooperating with different clinical and laboratory variables. Results: it was shown that the only characteristics that differ significantly between mutated and unmutated CLL were ALC count, b2micro, and risk group, high count ALC accounted for 62% and 32% had low count ALC in mutated CLL, unlike unmutated CLL in which most cases had high count ALC 80%. The risk group affected differed between mutated and unmutated CLL, with the latter being mostly found in the high-risk group ( 78% ). Another important aspect was that the survival probability of Unmutated CLL fell significantly more than Mutated CLL in the same amount of months, reaching almost zero in 180 months in unmutated CLL, unlike Mutated CLL, which fell to 0.50 then hitting a plateau. Another predictor of significant value is the trisomy 12 gene. The odds of unmutated CLL being detected as trisomy 12 is 387.6%. The study has a sensitivity of 68.2% and specificity of 68.7%, with a positive predictive value of 0.62 and a negative predictive value of 0.26.

Total RNA and genomic DNA were extracted simultaneously from peripheral blood mononuclear cells using QIAamp RNA Mini Kit and DNA extraction kit, following the manufacturer's protocol. The mutational status of the variable region of the immunoglobulin heavy chain (IGHV) gene is a robust biomarker that enables clinicians for prognostic purposes in CLL patients. Cases with mutated IGHV (mCLL) had a better prognosis, as seen above the survival probability in cases of mCLL is 0.50 in 150 months and continues to remain the same, unlike unmutated CLL in which the survival probability falls to 0.50 in 50 months reaching almost Zero in 180 months. Trisomy 12 and b2micro are significant predictors as they were found in most unmutated CLL. This is why karyotyping can be an essential tool. Furthermore, the clinical outcome and response to chemotherapy in mutated cases are better than in cases with unmutated IGHV. Therefore, it is paramount to identify mutation status early and elucidate the factors relating to the given status.

No relevant conflicts of interest to declare.