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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

doI 10.11603/IJMMR.2413-6077.2019.1.10305  

SIGNIFICANCE OF ADDITIONAL CHROMOSOMAL ABNORMALITIES  
FOR THE OUTCOMES AFTER THE SECOND LINE NILOTINIB THERAPY 
IN THE CHRONIC MYELOID LEUKEMIA PATIENTS

I.V. Dmytrenko*, Zh.M. Minchenko, V.V. Fedorenko, I.S. Dyagil 
NATIONAL RESEARCH CENTER FOR RADIATION MEDICINE OF THE NATIONAL ACADEMY  

OF MEDICAL SCIENCES OF UKRAINE, KYIV, UKRAINE 

Background. There is limited information about impact of additional chromosome aberrations (ACA) on 
the efficacy of the 2nd line nilotinib therapy. 

Objective. The aim of the study was to analyze significance of ACAs for the outcome after second line tyrosine 
kinase inhibitors (TKI) therapy with nilotinib in the chronic myeloid leukemia (CML) patients, who experienced 
previous imatinib therapy failure. 

Methods. The CML patients in chronic phase treated with nilotinib after imatinib failure were analyzed for 
outcomes. 

Results. Among a total of 114 patients, 18 patients (15.8%) had ACAs at the beginning of the 2nd line therapy 
with nilotinib. Seven patients (38.9%) of 18 had variant translocations and 11 patients (61.1%) had other 
chromosomal abnormalities in addition to t(9;22), known as clonal evolution. Complete cytogenetic response 
(CCR) at 12 months was achieved in 37.5%, 42.8% and 45.5% (p=0.842) of patients with classic t(9;22) translocation, 
variant translocations and ACAs respectively. In the patients with variant translocations t(9;V;22) or clonal evolution 
treated with nilotinib after the imatinib failure, the CCR and major molecular response (MMR), event free survival 
(EFS), progression free survival (PFS) and overall survival (OS) rates did not differ from those in the CML patients 
with t(9;22) only. At the same time quantitative characteristics of leukemic and ACA clones had prognostic value 
for CCR. The increased number of Ph-positive cells and the number of cells with the ACA at the start of nilotinib 
therapy reduced the probability of CCR. 

Conclusions. Higher nilotinib inhibitory activity compare with imatinib allows us to overcome imatinib 
resistance in the CML patients regardless of the ACA presence at the beginning of nilotinib therapy. 

KEY WORDS: additional chromosomal aberrations; chronic myeloid leukemia; nilotinib; second 
line of TKI therapy; prognosis; resistance.

*Corresponding Author: Iryna V. Dmytrenko, National Research
Center for Radiation Medicine of the National Academy of 
Medical Sciences of Ukraine, 119/121 Peremoha Avenue, Kyiv 
03115, Ukraine.
E-mail: iryna.v.dmytrenko@gmail.com 

Introduction
Reciprocal translocation t(9;22)(q34;q11.2), 

also known as Ph-chromosome, leads to the 
formation of the BCR/ABL1 fusion gene, which 
is considered to be the main pathogenetic event 
of chronic myeloid leukemia (CML) [1].

However, additional chromosomal abnor-
malities along with the classical translocation 
t(9;22) have been described in some patients 
with CML. These are usually either variant 
translocations or additional chromosome aber-
rations (ACAs). In case of variant translocation 
(t(9;V;22)), more than two chromosomes are 
involved in the formation of t(9;22). ACAs 
include any numerical or structural chromosome 
aberrations in addition to t(9;22) and are called 
clonal evolution. At the time of diagnosis, the 

frequency of ACAs is 5-10% in the patients with 
chronic phase CML and increases up to 30% and 
80% in the patients with acceleration phase or 
blast crisis [2, 3]. A de-novo gain of ACA during 
the therapy is also possible. It is established 
that ACAs confer a BCR/ABL-independent 
mechanism of resistance to the therapy with 
tyrosine kinase inhibitors (TKI) [4]. Although, 
currently, there is no final consensus about the 
predictive value of ACAs, most authors point 
out that the outcome of imatinib-treated 
patients with ACAs is significantly lower than of 
those without ACAs [5, 6].

It has been proved that nilotinib (the second 
generation TKI) is effective in patients with CML 
after imatinib failure [7, 8]. But the influence of 
nilotinib on leukemic clones with additional 
chromosomal abnormalities has not been 
determined. 

The objective of this study was to analyze the 
significance of ACAs for the outcome after 
second line TKI therapy with nilotinib in the CML 

International Journal of Medicine and Medical Research 
2019, Volume 5, Issue 1, p. 33-39
copyright © 2019, TNMU, All Rights Reserved

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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

patients, who experienced previous imatinib 
therapy failure. 

Methods
A retrospective study of 114 CML patients 

in chronic phase treated with nilotinib after 
imatinib failure was conducted. All patients 
were monitored at the Department of Radiation 
Onco-Hematology and Stem Cell Transplantation 
of the Institute of Clinical Radiology at the 
National Research Center for Radiation Me-
dicine from 2008 to 2018. written informed 
consents to use biomaterial for the research 
purposes were obtained from all patients. 
Among a total of 114 patients, 49 (43%) were 
males and 51 (57%) – females. Imatinib for the 
first line TKI therapy was administrated at a 
dose of 400 mg/d with later escalation to 
800 mg/d. The second line TKI therapy was 
implemented with nilotinib dose 400 mg twice 
a day. 

Cytogenetic analysis was conducted at the 
time of imatinib resistance conformation. 
Karyo typing with standard GTG-banding was 
performed after a 24-hour bone marrow cells 
culture with no stimulation. Chromosomes 
were classified according to the International 
System for Human Cytogenetic Nomencla-
ture [9].

Molecular response was assessed in 3, 6 12 
months and then every 6 months during 
nilotinib therapy by real-time polymerase chain 
reaction as previously reported [10]. A complete 
cytogenetic response (CCR), major molecular 
response (MMR) and deep molecular response 
(MR4) were defined as BCRABL1/ABL ratios 1%, 
0.1%, and 0.01% respectively, on the interna-
tional scale. The first and second line TKI the-
rapy responses and resistance were defined 
according to the ELNet 2013 recommenda-
tions [6].

The χ2 test and Fisher’s exact test were used 
to compare categorical variables and the 

Mann–whitney U-test – to compare continuous 
variables. The probability of overall survival 
(OS), progression free survival (PFS), and event 
free survival (EFS) were estimated by the 
Kaplan-Meier method and compared by the 
log-rank test. PFS was defined as survival 
without signs of progression (transformation 
into acceleration phase or blast crisis). EFS was 
evaluated from the beginning of the 2nd line 
therapy with nilotinib to the loss of achieved 
CCR or MMR, progression or death for any 
cause. OS was assessed from the beginning of 
the 2nd line therapy till the death of any cause 
during the study. The cumulative probability of 
CCR and MMR was evaluated by the Kaplan–
Meier method from the beginning of the 2nd 
line therapy to the time of response. In this 
case, the data about the patients, who had not 
received any adequate response, with pro-
gressed disease or died, were censored at the 
latest observation date. Univariate analyses 
(Cox regression) were performed to evaluate 
the prognostic significance of additional 
chromosomal abnormalities. Statistical analysis 
was performed using the SPSS for windows 
statistical software package (version 20.0). The 
results were considered significant at p<0.05.

Results
The baseline characteristics of the patients 

are summarized in Table 1. 
Among 114 patients, who started the 

second line therapy with nilotinib, 101 (88.9%) 
were resistant to previous imatinib therapy. 
Resistance was defined as failure to achieve 
CCR on the first line of therapy. Twelve patients 
(10.5%) achieved only CCR, while 1 (0.9%) 
patient achieved MMR with previous imatinib 
therapy. Any achieved therapy response was 
completely lost in all patients with CCR and 
MMR by the start of nilotinib. Pathologic clone 
with classical t(9:22)(q34;q11) was detected in 
5-100% of cells of all patients at the time of the 

Table 1. CML patients’ characteristics at the start of the 2nd line therapy with nilotinib

Patient characteristics Patients with only t(9;22) (n=96)
Patients with 
t(9;V;22) (n=7)

Patients with 
ACA (n=11) р

Age, median (range), years 38 (18–66) 38 (34–50) 35 (20 – 52) 0.512
Sex, men, n (%) 40 (41.7) 3 (42.9) 6 (54.5%) 0.950
Median of prior imatinib 
treatment, (range), months

44.0
(4.0–106.0)

39,0
(13.0–48.0)

45.0
(5.0–106.0) 0.578

Median of follow-up on the 
2nd line therapy with nilotinib, 
(range), months

52.0
(4.0–106.0)

42.0
(5.0–97.0)

32.0
(1.0–79.0)

0.194

Notes: CML – chronic myeloid leukemia; ACA – additional chromosomal aberration

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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

second-line therapy initiation. The median 
number of Ph-positive cells with variant 
translocation or with an ACA was 15% (range 
of 5-100%). The median duration of prior 
imatinib treatment was 43 months (range of 4 
to 106 months), while the median duration of 
the second-line therapy monitoring was 47 
months (range of 1 to 106 months).

Among a total of 114 examined patients, 18 
patients (15.8%) had ACAs at the beginning of 
the 2nd line therapy with nilotinib. Seven 
patients (38.9%) of 18 had variant translocations 
and 11 patients (61.1%) had other chromosomal 
abnormalities in addition to t(9;22). Among the 
other 11, 8 patients had a single chromosomal 
abnormality in addition to t(9;22), while 3 
patients had multiple chromosomal abnor-
malities. In the majority of patients with ACAs 
(7 out of 11, 63.6%), an additional translocation 
was a second Ph-chromosome (Table 2). The 
patients with an isolated t(9;22) translocation, 
variant translocations or ACA were not sig-
nificantly different by age, sex, and length of 
treatment before the beginning of the second-
line therapy. 

In order to evaluate the effect of ACAs on 
response to the second-line TKI therapy, the 
extent of tumor clone reduction in 12 months 
of therapy, the probability of CCR and MMR, as 
well as long-term outcomes (EFS, PFS and OS) 
were evaluated in all 114 patients with CML, 
treated with nilotinib after imatinib failure.

The presence of ACAs and variant trans-
locations at the beginning of the 2nd line therapy 
did not affect the rate of the tumor clone re-
duction. The CCR in 12 months (optimal res-
ponse according to ELNet2013) was achieved 
in 37.5%, 42.8% and 45.5% (p=0.842) of patients 
with classic t(9;22) translocation, variant 
translocations and ACAs respectively. In 12 
months, about 50% of patients were resistant 
to the second line TKI therapy (BCR/ABL>10% 
in 12 months of the therapy according to 
ELNet2013). The rate of resistance did not differ 
between the groups: 51.0%, 57.1% and 54.5% 
in the patients with classic t(9;22) translocation, 
variant translocations and ACAs, respectively 
(Table 3).

No differences in the rates of disease 
progression and lethal outcomes were found 

Table 2. Karyotypes of bone marrow cells with variant translocations and additional  
chromosomal aberrations in the CML patients at the beginning of nilotinib therapy (n=18)

№ Sex Number of Ph+ metaphases, %

Number of 
metaphase 
with ACA, %

Karyotype

1 F 95 100 46,ХХ,t(9;22;?)(q34;q11;?)[19] 46,ХХ[1]
2 F 100 100 46,ХХ,t(5;9;22)( q31;q34;q11)[20]
3 F 100 5 46,ХХ,t(9;22)(q34;q11)[19]/idem,+der(22)t(9;22) [1]
4 M 73 53,3 46,XY,t(9;22)(q34;q11)[3]/idem,+der(22)t(9;22)[8]/46,Xy[4]
5 M 100 100 46,Xy,t(6;9;22)(р22;q34;q11)[20]
6 F 100 100 46,ХХ,der(9)t(9;?;22)(q34;?;q11)[20]
7 M 85 5 46,ХY,t(9;22)(q34;q11)[5]/ idem,+der(22)t(9;22)

[1]/46,ХY[14]
8 M 100 70 46,ХY,t(9;22)(q34;q11)[6]/idem,+der(22)t(9;22)[11]/ 

idem,+der(22)t(9;22),+7[3]
9 M 100 100 47,XY,t(9;22)(q34;q11),+der(22)t(9;22)[14]/ idem,+12[2]

10 F 50 42,5 47,XX,t(9;22)(q34;q11),+der(22)t(9;22)[17]/ 46,XX,t(9;22)
(q34;q11)[13]/46,XX[20]

11 M 30 30 46, ХY,t(3;9;22)(р25;q34;q11)[6] /46,ХY[14]
12 F 100 30 47,ХХ,t(9;22)(q34;q11),+3[6]/ 46,ХХ,t(9;22)(q34;q11)[14]
13 M 20 100 46~48,XY,t(9;22)(q34;q11)[4],del(10)(p11.2)[5], 

+12[2],+13[12],+14[2]+15[4] [cp20]
14 F 100 100 46,ХХ,t(3;21)(q26.2;q22),t(9;22)(q34;q11)[20]
15 M 100 100 46,ХY,t(9;21;22;)(q34; q22.2;q11)[20]
16 F 100 5 46,ХХ,t(9;22)(q34;q11)[19]/idem,+der(22)t(9;22)[1]
17 M 90 5 46,ХY,t(9;22)(q34;q11)[17]/

idem,+der(22)t(9;22)[1]/46,Xy[2]
18 F 100 100 46,ХХ,t(1;9;22)(q21.2;q34;q11)[20]

Notes: ACA – additional chromosomal aberration.

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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

between the patients with classic t(9;22) 
translocation, variant translocations and ACAs 
(Table 3). For the whole follow-up period, the 
only case of progression to accelerated phase 
with a lethal outcome took place in one patient 
with variant translocation of unknown origin 
t(9;?;22)(q34;?;q11) and in one patient with 
three related clones: 30% metaphases with 
isolated Ph-chromosome, 55% metaphases 
with an additional Ph-chromosome, and 15% 
of metaphases with two Ph-chromosomes and 
an extra chromosome 7. Karyotype 46,ХY,t(9;22)
( q 3 4 ; q 1 1 ) [ 6 ] / i d e m , + d e r ( 2 2 ) t ( 9 ; 2 2 ) [ 1 1 ] /
idem,+der(22)t(9;22),+7[3].

Kaplan-Meier analysis of the long-term 
outcomes of the 2nd line nilotinib therapy 
proved an absence of significant influence of 
the ACA and variant translocation status at the 
beginning of the 2nd line nilotinib therapy on 
the three-year EFP, PFS and OS (Table 4).

Despite the ACAs at the beginning of the 2nd 
line therapy did not affect the nilotinib efficacy, 
quantitative characteristics of the leukemic 
clone did have prognostic value. A positive 

correlation between the amount of Ph-positive 
clone before the beginning of the 2nd line 
nilotinib therapy and development of resistance 
(BCR/ABL1>10%) in 12 months of the subsequent 
therapy (Spearman correlation coefficient 
r=0.423, p<0.001) was found. The increase in 
the number of Ph-positive cells at the beginning 
of the nilotinib therapy and increase in size of 
the additional clone (percent metaphases with 
ACA) was associated with the decreased 
efficiency of tumor clone reduction during the 
therapy, or more specifically, statistically 
significant decrease in the rate of CCR (p<0.001, 
p=0.049). In other words, the efficacy of the 
second line TKI therapy in the imatinib-resistant 
CML patients was associated with the level of 
reduction of the tumor clone and the size of the 
clone with additional aberrations before the 
beginning of the second-line therapy (Table 5).

Discussion
Studies of the ACA prognostic value both in 

the era before the TKI and after approving of 
the first TKI imatinib indicate that the ACA 

Table 3. Response to the 2nd line nilotinib therapy in the CML patients depending  
on the presence of additional chromosomal aberrations 

Characteristics
Patients with 
only t(9;22) 

(n=96)

Patients with 
t(9;V;22) (n=7)

Patients with 
ACA (n=11) р

Response in 12 months of the 2nd line 
nilotinib therapy:
CCR (BCR/ABL1≤1%), n (%)
MMR (BCR/ABL1≤0.1%), n (%)
BCR/ABL1>10%, n (%)

36 (37.5)
13 (13.5)
49 (51.0)

3 (42.8)
1 (14.3)
4 (57.1)

5 (45.5)
3 (27.3)
6 (54.5)

0.842
0.516
0.938

Secondary resistance:
MMR loss, n (%)
CCR loss, n (%)
Progression to AP or BC, n (%)

4/30 (13,3)
4/46 (8.7)
19 (19.8)

0/2 (0)
0/4 (0)
1 (14.3)

1/5 (20)
0/5 (0)
2 (18.2)

0.829
0.656
0.934

Number of lethal outcomes, n (%) 17 (17.7) 1 (14.3) 1 (9.1) 0.756

Notes: CML – chronic myeloid leukemia; ACA – additional chromosomal aberration; CCR – complete cyto-
genetic response; MMR – major cytogenetic response, AP – acceleration phase; BC – blast crisis. 

Table 4. Long-term outcomes of the 2nd line nilotinib therapy in the CML patients depending  
on the presence of additional chromosomal aberrations

Outcomes Patients with only t(9;22) (n=96)
Patients with 
t(9;V;22) (n=7)

Patients with ACA 
(n=11) р

3-year ЕFS, % (95% CІ) 80.1
(71.5–88.7)

80.0
(45.5–100.0)

74.1
(42.5–100.0)

0.468

3-year PFS, % (95% CІ) 86.4
(79.1–93.7)

80.0
(45.5–100.0)

76.2
(47.2–100.0)

0.936

3-year ОS, % (95% CІ) 90.7
(84.6–96.8)

80.0
(45.5–100.0)

85.7
(59.8–100.0)

0.975

Notes: CML – chronic myeloid leukemia, ACA – additional chromosomal aberration, CI – confidence interval, 
EFS – event free survival, PFS – progression free survival, OS – overall survival.

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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

presence in the therapy worsens the treatment 
results and decreases patient survival [11–13]. 
S o m e  d i s a g r e e m e n t s  a r e  o b s e r v e d  i n 
assessment of the ACA significance at the time 
of diagnosis. Alhuraiji A., et al. in the prospective 
clinical study on 603 CP CML patients pointed 
out that the presence of ACA at the time of 
diagnosis was not associated with worse 
prognosis [14]. Fabarius, et al. consider that 
o n l y  m a j o r  ro u t e ,  b u t  n o t  b a l a n c e d  o r 
unbalanced minor route ACA has a negative 
impact on prognosis of CML [13]. wang et al. 
also underline that variability in outcomes is 
related to the type of ACA, but they suggest 
another ACA stratification system. ‘Poor 
prognosis’ for ACA including i(17)(q10), -7/
del7q, and 3q26.2 rearrangements as well as 
presence of 2 or more ACAs conferred a worse 
survival irrelevant to the emergence phase and 
time. In contrast, ACAs in group of ‘good 
prognosis’ including trisomy 8, -y, and an extra 
copy of Ph-chromosome had no adverse impact 
on survival, when they emerged at the chronic 
phase or at the time of CML diagnosis [15].

Nilotinib is more potent and selective ATP-
competitive inhibitor of BCR/ABL1 tyrosine 
kinase than imatinib and it is more active 
against imatinib-resistant mutant forms of 
enzyme [16, 17]. Multicenter trials and a real-life 
longitudinal proved nilotinib efficacy in the CML 
patients with imatinib failure [8, 18]. 

Our report presents outcomes after the 
second line therapy with nilotinib in the CML 
patients with imatinib failure depending on the 
presence of variant translocations or clonal 
evolution at the beginning of the 2nd line 
therapy with nilotinib. Among a total of 114 
examined patients, 18 patients (15.8%) had 
clonal evolution at the beginning of nilotinib. 

Seven patients (38.9%) of 18 had variant 
translocations and 11 patients (61.1%) had 
c l o n a l  ev o l u t i o n  –  a d d i t i o n a l  t o  t ( 9 ; 2 2 ) 
chromosomal abnormalities. Our results 
suggest that for the patients with variant 
translocations t(9;V;22) or clonal evolution 
treated with nilotinib after imatinib failure, the 
CCR and MMR response, EFS, PFS and OS rates 
do not differ from those of the CML patients 
with t(9;22) only. At the same time quantitative 
characteristics of leukemic and ACA clones have 
a significant impact on CCR. The greater 
number of Ph-positive cells and the number of 
cells with the ACA are revealed at the beginning 
of nilotinib, the less – for CCR probability. EFS 
is also worse with increasing number of Ph-
positive cells at the beginning of nilotinib. The 
significance of certain types of ACA for long-
term outcomes has not been investigated 
because of small groups of patients with 
different ACAs.

Conclusions
The presence of ACA provides the tumor 

with heterogeneous properties that determine 
its sensitivity to therapy. But higher inhibitory 
activity of nilotinib compare to the imatinib 
allows overcoming imatinib resistance in the 
CML patients regardless of the ACA presence 
and achieves CCR in about 50 % of patients in 
12 months of nilotinib therapy. Investigation of 
prognostic value of the combination ACA with 
other tumor clone features advantages 
development of criteria for the individual 
selection of TKI in the resistant patients.

Conflicts of Interest 
Authors declare no conflict of interest.

Table 5. Estimation of the significance of ACA clones quantitative characteristics in the CML 
patients (n=18) at the beginning of the 2nd line nilotinib therapy for the probability of CCR, EFS, PFS 

and OS by the univariate Cox regression analyses

Characte-
ristics

CCR ЕFS РFS OS
Exp(B)

(95% CI) р
Exp(B)

(95% CI) р
Exp(B)

(95% CI) р
Exp(B)

(95% CI) р

% Ph+ 
metaphases

0.981
(0.971–0.990)

<0.001 1.027
(1.00–1.054)

0.039 1.037
(1.000–1.076)

0.052 1.062
(0.997–1.132)

0.062

% meta-
phases with 
ACA

1.041
(1.000–.083)

0.049 1.028
(0.979–1.080)

0.268 1.031
(0.979–1.085)

0.248 1.025
(0.973–1.080)

0.354

Notes: CML – chronic myeloid leukemia; ACA – additional chromosomal aberration; CI – confidence interval; 
EFS – event free survival; PFS – progression free survival; OS – overall survival.

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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

зНАЧЕННЯ ДОДАТКОВИХ ХРОМОСОМНИХ АБЕРАЦІй У ФОРМУВАННІ
ВІДПОВІДІ НА ДРУГУ ЛІНІЮ ТЕРАПІЇ НІЛОТИНІБОМ У ХВОРИХ НА 
ХРОНІЧНУ МІєЛОЇДНУ ЛЕйКЕМІЮ

І.В. Дмитренко, Ж.М. Мінченко, В.Г. Федоренко, І.С. Дягіль 
ДУ “НАцІОНАЛьНий НАУКОВий цЕНТР РАДІАцІйНОї МЕДициНи НАцІОНАЛьНОї  

АКАДЕМІї МЕДиЧНиХ НАУК УКРАїНи”, КиїВ, УКРАїНА 

Вступ. Існує обмежена інформація про вплив додаткових хромосомних аберацій (ДХА) на ефективність 
терапії нілотінібом другої лінії у хворих з хронічною мієлодною лейкемією (ХМЛ).

Мета: проаналізувати значущість ДХА щодо відповіді на терапію інгібіторами тирозинкіназ (ІТК) 
другої лінії (нілотинібом) у хворих на ХМЛ, у яких терапія іматинібом була неефективною.

Методи. Аналізували ефективність терапії нілотинібом у хворих на ХМЛ в хронічній фазі, у яких 
терапія іматинібом була неефективною.

Результати. Серед 114 пацієнтів 18 пацієнтів (15,8%) мали ДХА на початку 2-ї лінії терапії 
нілотінібом. Сім пацієнтів (38,9%) з 18 мали варіантні транслокації, а 11 пацієнтів (61,1%) мали інші 
хромосомні аномалії, крім t(9;22), тобто ознаки клональної еволюції. Повна цитогенетична відповідь 
(ПцВ) через 12 місяців терапії нілотинібом була досягнута у 37,5%, 42,8% і 45,5% (p=0,842) пацієнтів з 
класичною транслокацією t(9;22), варіантними транслокаціями та клональною еволюцією відповідно. 
У пацієнтів з варіантнимии транслокаціями t(9;V;22) та клональною еволюцією швидкість ПцВ та 
великої молекулярної відповіді (ВМВ), безподійна виживаність (EFS), виживаність без прогресії (PFS) та 
загальна виживаність (ОS) не відрізнялися від таких у хворих на ХМЛ, у яких виявлялась тільки 
транслокація t(9;22). В той же час, кількісні характеристики лейкемічного клону та клону з ДХА мали 
прогностичне значення щодо досягнення ПцВ. Збільшення кількості Ph-позитивних клітин та клітин 
з ДХА на початку терапії нілотинібом зменшувало вірогідність досягнення ПцВ.

Висновки. Більш висока інгібуюча активність нілотинібу в порівнянні з іматинібом дозволяє 
подолати резистентність до іматинібу у пацієнтів з ХМЛ незалежно від наявності ДХА на початку 
терапії нілотинібом.

КЛЮЧОВІ СЛОВА: додаткові хромосомні аберації; хронічна мієлоїдна лейкемія; нілотиніб; 
друга лінія терапії ІТК (інгібітори тирозинкіназ); прогнозування; резистентність.

Інформація про авторів 
Дмитренко Ірина Віталіївна – канд. біол. наук, старший науковий співробітник лабораторії 
імуногенетики відділу гематології та трансплантології, ДУ “Національний науковий центр радіаційної 
медицини Національної академії медичних наук України”.
Мінченко Жанна Миколаївна – д-р біол. наук, професор, завідувач лабораторії імуногенетики відділу 
гематології та трансплантології, ДУ “Національний науковий центр радіаційної медицини Національної 
академії медичних наук України”.
Федоренко Віра Григорівна – молодший науковий співробітник лабораторії імуногенетики відділу 
гематології та трансплантології, ДУ “Національний науковий центр радіаційної медицини Національної 
академії медичних наук України”.
Дягіль Ірина Сергіївна – д-р мед. наук, завідувач відділення радіаційної онкогематології та 
трансплантації стовбурових клітин відділу гематології та трансплантології, ДУ “Національний науковий 
центр радіаційної медицини Національної академії медичних наук України”.

Information about the authors
Iryna V. Dmytrenko – Ph.D., Senior Researcher, Immunogenetic Laboratory, Hematology and 
Transplantology Department, State Institution “National Research Center for Radiation Medicine of the 
National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine. 
ORCID 0000-0002-2136-5442, e-mail: iryna.v.dmytrenko@gmail.com
Zhanna M. Minchenko – Doctor of Biological Science, Professor, Head of the Immunogenetic Laboratory, 
Hematology and Transplantology Department, State Institution “National Research Center for Radiation 
Medicine of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine.
Vira V. Fedorenko – Researcher, Immunogenetic Laboratory, Hematology and Transplantology Department, 
State Institution “National Research Center for Radiation Medicine of the National Academy of Medical 
Sciences of Ukraine”, Kyiv, Ukraine.
Iryna S. Dyagil – Doctor of Medical Science, Head of the Radiation Oncohematology and Transplantology 
Department, State Institution “National Research Center for Radiation Medicine of the National Academy 
of Medical Sciences of Ukraine”, Kyiv, Ukraine.

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iSSn 2413-6077. iJMMR 2019 Vol. 5 issue 1

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Received 05 May 2019; revised 19 May 2019;  
accepted 05 June 2019.

This is an open access article distributed under the Creative 
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distribution, and reproduction in any medium, provided the 
original work is properly cited. 

I.V. dmytrenko et al.