Objective: Assess the influence of e13a2 and e14a2 transcripts of BCR/ABL1 gene on the efficiency of imatinib ther apy in patients with chronic myeloid leukemia.
Materials and methods: We examined 508 patients with the chronic phase of chronic myeloid leukemia without radi ation in anamnesis as well as 13 patients with the similar diagnosis and with confirmed presence of radiation expo sure due to the Chornobyl Nuclear Power Plant accident.
Results: No significant differences in hematologic parameters, rate of additional chromosomal aberrations and f vari ant translocations were observed between patients with е13а2 and е14а2 transcript. Cumulative probability of com plete cytogenetic response did not differ in patients with е13а2 and е14а2 transcript and was 76 and 80 % respec tively (р = 0,981). Median of achieving a complete cytogenetic response was 20 months in both patient groups. Significantly more patients with e14a2 transcript compared to patients with e13a2 achieved major molecular response by 12 month of therapy (61.5 % versus 23.0 %, p = 0.016). The higher incidence of deep molecular response by 24 month of therapy was revealed in this group (38.7 % versus 6.25 %, p = 0.018). The overall survival and pro gression free survival rates were not statistically different between two groups with different transcripts. However, the rate of event free survival was statistically lower for the patients with e13a2 transcript compared to the ones with e14a2 transcript (51 % versus 62.0 %, p = 0.039). The number of primary resistant patients was 40 % regardless of the transcript expressed. A significant prevalence in incidence either of lost complete cytogenetic response or fail ure of the major molecular response was shown in patients with e13a2 transcript compared to patients with e14a2 transcripts (43.5 % versus 24.8 %, p = 0.015).
Conclusion: Imatinib therapy is more effective for CML patients with e14a2 transcript compared to patients with e13a2 transcript expression. The transcript e13a2can be viewed as a adverse prognostic factor for imatinib therapy of chronic myeloid leukemia.
Meta – doslidzhennia vplyvu e13a2 ta e14a2 transkryptiv gena BCR/ABL1 na efektyvnist' terapiI imatynibom u khvorykh na khronichnu miieloIdnu leykemiiu.Materialy i metody. Obstezheno 508 patsiientiv z khronichnoiu fazoiu khronichnoI miieloIdnoI leykemiI bez radiatsiynogo anamnezu, a takozh 13 patsiientiv z takym zhe diagnozom, u iakykh bulo dokumental'no pidtverdzheno na iavnist' radiatsiynogo vplyvu vnaslidok avariI na ChAES.Rezul'taty. Ne vyiavleno znachushchykh rozbizhnostey u gematologichnykh pokaznykakh, rivni dodatkovykh khromosomnykh aberatsiy ta chastoti variantnykh translokatsiy mizh patsiientamy, u iakykh ekspresuvalysia transkrypty e13a2 ta e14a2. Kumuliatyvna virogidnist' povnoI tsytogenetychnoI vidpovidi ne vidriznialas' u patsiientiv z e13a2 ta e14a2 transkryptom i skladala 76 ta 80 %, vidpovidno (r = 0,981). Mediana chasu dosiagnennia povnoI tsytogenetychnoI vidpovidi – 20 misiatsiv u obokh grupakh. Sered patsiientiv z e14a2 virogidno bil'sha chastyna do 12 go misiatsia terapiI otrymala velyku molekuliarnu vidpovid' (61,5 % proty 23,0 %, r = 0,016). A do 24 go misiatsia same v tsiy grupi patsiientiv reiestruvalosia bil'she vypadkiv glybokoI molekuliarnoI vidpovidi (38,7 % proty 6,25 %, r = 0,018). Ne vyiavleno statystychno znachushchykh vidminnostey u zagal'niy vyzhyvanosti ta u vyzhyvanosti bez progresiI u patsiientiv z riznymy typamy transkryptiv. Bezpodiyna vyzhyvanist' u patsiientiv z e13a2 transkryptom bula virogidno nyzhcha porivniano z patsiientamy z e14a2 transkryptom (52 % proty 61,0 %, r = 0,039). Kil'kist' pervyn no rezystentnykh patsiientiv ne zalezhala vid typu transkryptu i skladala ponad 40 %. U patsiientiv z e13a2 tran skryptom bulo vyiavleno statystychno virogidne perevazhannia vypadkiv vtraty dosiagnutoI povnoI tsytogenetychnoI vidpovidi abo nedosiagannia velykoI molekuliarnoI vidpovidi (43,5 % proty 24,8 %, r = 0,015).Vysnovky. Terapiia imatynibom ie bil'sh efektyvnoiu u khvorykh na KhML z e14a2 transkryptom porivniano z patsiientamy iz e13a2 transkryptom. Transkrypt e13a2 mozhna rozgliadaty iak nespryiatlyvyy prognostychnyy fak tor pry terapiI imatynibom u patsiientiv z khronichnoiu fazoiu khronichnoI miieloIdnoI leykemiI.
Keywords: chronic myeloid leukemia; cytogenetic and molecular responce; imatinib; ionizing radiation; therapy efficeincy; е13а2 and е14а2 transcripts.
I. V. Dmytrenko, V. G. Fedorenko, T. Y. Shlyakhtychenko, V. V. Sholoyko, T. F. Lyubarets, T. V. Malinkina, O. O. Dmytrenko, V. V. Balan, S. M. Kravchenko, Z. V. Martina, A. O. Tovstogan, J. M. Minchenko, I. S. Dyagil.