Aim: In chronic myeloid leukemia (CML), the impact of MBCR-ABL1 major transcript type on disease phenotype and response to treatment still controversial to date. This work aims to study the influence of Mb3a2 and Mb2a2 transcripts on clinico-biological parameters and the molecular response in patients with chronic phase chronic myeloid leukemia (CP-CML) treated with Imatinib as frontline therapy. Methods: This is six years prospective study started in March 1 st, 2013. 67 patients with newly CP-CML were treated by Imatinib as frontline therapy. Clinical and biological characteristics disease were collected for all patients. Molecular typing was performed by multiplex RT-PCR and quantification of transcripts by real-time quantitative PCR (qRT-PCR). The cumulative incidence of deep molecular response (DMR) was estimated by the Kaplan-Meier method. The comparison was made using the parametric Log-Rank test. A value of P ≤ 0.05 is considered significant. Results: 61% of patients expressed b3a2, 35.82% b2a2 and 2.98% expressed a rare transcript of type e19a2. At diagnosis, the b2a2 type had a higher level of expression than that of b3a2 (67.92 vs 53.79%; P ¼ 0.03). This insignificant difference between the two transcript subgroups was also observed for rates below 1% at 6 months (54 vs 39; P ¼ 0.26) and below 0.1% (54 vs 44 %; P ¼ 0.50), (77 vs 50%; P ¼ 0.09) and (81 vs 78 %; P ¼ 0.52) at 12, 18 and 24 months respectively. The two types of transcript had almost the same kinetics. Nevertheless, the absolute value of the BCR-ABL1/ABL ratio decrease was faster in the group of patients expressing b3a2, than in those expressing b2a2. At 18 months post IM therapy, patients with a b3a2 transcript have a trend of better MMR that those with b2a2 (77 vs 50%; P ¼ 0.09). The DMR was not significantly different between two groups at 24 months (50 vs 32%; P ¼ 0.20) and 36 months (75 vs 70%; P ¼ 0.54) respectively. The cumulative probability of achieving MRD at 5 years was higher in patients with b3a2 type but not statistically significant; (85 vs. 68%; P ¼ 0.17). Conclusion: Patients with b3a2 transcript may be associated with a better response to Imatinib therapy.
Nachi, Mourad; Kihel, Ibtissem; Entasoltane, Badra; Brahimi, Mohamed; Yafour, Nabil; Guella, Djaoued; Abed, Amine; and Bekadja, Mohamed A.
"Impact of the Major BCR-ABL1 Transcript Type on Clinical and Biological Parameters and Molecular Response in Patients With Chronic Myeloid Leukemia,"
Hematology/Oncology and Stem Cell Therapy: Vol. 15
, Article 9.
Available at: https://doi.org/10.1016/j.hemonc.2020.08.003
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