EXPRESSION PROFILE OF TRANSCRIPTION FACTORS IN THE BLOOD SAMPLES OF PATIENTS WITH THE CHRONIC LYMPHOCYTIC LEUKEMIA
Keywords:
chronic lymphocytic leukemia, transcription factors, gene expression profile.Abstract
Summary. Aim: to investigate the expression profile
of transcription factors in chronic lymphocytic leukemia
(CLL) cells compared with B cells to identify mechanisms
of CLL appearance. Objects and methods: Samples of peripheral blood of patients with CLL, RNA isolation, analysis of expression of transcription factors, using RT2
profiler Array and quantitative polymerase chain reaction. Results: using the PARN-075Z platform, expression of the 84
transcription factors was studied in a mixture of RNA isolated from CLL cells of patients, in comparison B cells and
a mixture of RNA isolated from B- and T-cells of healthy
donors. We have found that genes POU2ATF1, NFAT5,
NFATC1, JUNB, JUN, and RELB were expressed at higher levels in a mixture of RNA from CLL cells when compared with B-cells. Using quantitative polymerase chain
reaction, we have observed that genes HAND1, HOXA5,
and SMAD9 were similarly expressed in CLL cells of individual patients while the ID1 gene, in contrast, showed
a higher expression compared with normal B-cells. Conclusions: the expression of the 84 transcription factors was
studied in a mixture of RNA isolated from cells of CLL
patients, compared with B cells from healthy donors. Given the heterogeneity of patients, gene expression was analyzed in samples of individual patients. It was confirmed
that genes HAND1, HOXA5, and SMAD9 expressed at low
levels in CLL cells of individual patients, unlike genes ID1
and JUNB that showed a heterogeneous pattern of expression. A clear difference in expression profiles allows us to
extend our research to identify cellular pathways blocked
in CLL cells, using bioinformatics analysis.
References
Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA
Cancer J Clin 2010; 60 (5): 277–300.
Глузман ДФ, Скляренко ЛМ, Надгорная ВА. Диагностическая онкогеамтология. Киев: ДИА, 2011. 256 с.
Gaidano G, Foà R, Dalla-Favera R. Molecular pathogenesis of chronic lymphocytic leukemia. J Clin Invest 2012; 122
(10): 3432–8.
Chiorazzi N, Ferrarini M. Evolving view of the in vivo kinetics of
chronic lymphocytic leukemia B cells. Hematology 2006; (1): 273–8.
Messmer BT, Messmer D, Allen S L, et al. In vivo measurements document the dynamic cellular kinetics of chronic lymphocytic leukemia B cells. J Clin Invest 2005; 115 (3): 755–64.
Hallek M, Cheson BD, Catovsky D, et al. Guidelines for
the diagnosis and treatment of chronic lymphocytic leukemia: a
report from the International Workshop on Chronic Lymphocytic
Leukemia updating the National Cancer Institute-Working Group
guidelines. Blood 2008; 111 (12): 5446–56.
Dighiero G, Hamblin TJ. Chronic lymphocytic leukaemia.
Lancet 2008; 371 (9617): 1017–29.
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision
of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127: 2375–90.
Savli H, Sunnetci D, Cine N, et al. Gene expression profiling of B-CLL in Ukrainian patients in post-Chernobyl period. Exp
Oncol 2012; 34 (1): 57–63.
Savli H, Akkoyunlu RU, Gine N, et al. Deregulated levels
of the NF-ΚB1, NF-ΚB2, and REL genes in Ukrainian patients
with leukemia and lymphoma in the post-Chernobyl period. Turk
J Hematol 2016; 33 (1): 8–14.
Knöfler M, Meinhardt G, Bauer S, et al. Human Hand1 basic helix-loop-helix (bHLH) protein: extra-embryonic expression
pattern, interaction partners and identification of its transcriptional repressor domains. Biochem J 2002; 361 (3): 641–51.
Lee DH, Forscher C, Di Vizio D, Koeffler HP. Induction
of p53-independent apoptosis by ectopic expression of HOXA5 in
human liposarcomas. Sci Rep 2015; 5 (Article No. 12580). 11 p.
Sun XH, Copeland NG, Jenkins NA, et al. Id proteins
Id1 and Id2 selectively inhibit DNA binding by one class of helixloop-helix proteins. Mol Cell Biol 1991; 11 (11): 5603–11.
Sun XH. Constitutive expression of the Id1 gene impairs
mouse B cell development. Cell 1994; 79 (5): 893–900.
Fan SJ, Li HB. miRNA-149 promotes cell proliferation
and suppresses apoptosis by mediating JunB in T-cell acute lymphoblastic leukemia. Leuk Res 2016; 41 (2): 62–70.