Clinical Value of miR-3151 Overexpression in Synergistic Interaction with BAALC Host Gene in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation

AI Shakirova, IM Barkhatov, AI Churkina, NN Mamaev, LS Zubarovskaya, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Oncology, Hematology and Transplantation; IP Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Alena Igorevna Shakirova, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)338-62-72; e-mail: alyona.i.shakirova@gmail.com

For citation: Shakirova AI, Barkhatov IM, Churkina AI, et al. Clinical Value of miR-3151 Overexpression in Synergistic Interaction with BAALC Host Gene in Patients with Acute Myeloid Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation. Clinical oncohematology. 2019;12(3):303–8 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-303-308


ABSTRACT

Background. Among a multitude of molecular genetic changes underlying acute myeloid leukemia (AML) disordered epigenetic regulation is of special importance. It includes expression change in miR-3151 gene forming a part of BAALC gene on chromosome 8 in q22.3 locus. At present BAALC gene overexpression is observed in a half of AML patients. A considerable part of them shows a combination of it with an increased transcriptional activity of miR-3151 gene, which is associated with the poorest AML prognosis.

Aim. To assess the prognostic value of miR-3151 overexpression in synergistic interaction with BAALC host gene in AML patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. The trial included bone marrow samples taken from 10 healthy SCT donors and 29 AML patients after receiving allo-HSCT. Relative miR-3151 expression level and relative BAALC copy number were measured by quantitative real-time polymerase chain reaction.

Results. The analysis yielded a poor correlation between miR-3151 expression level and blast cell count in bone marrow (r = 0.330; = 0.005) as well as between the expression levels of miR-3151 and BAALC (r = 0.273; = 0.020). In addition, a great prognostic value of miR-315 overexpression in post-transplantation period was confirmed (= 0.005). Patients with miR-315 and BAALC co-expression in post-transplantation period have also the poorest prognosis than the control group with regard to both disease-free survival and relapse risks within 2 years after allo-HSCT.

Conclusion. Monitoring expression level of miR-3151 and its host gene BAALC in AML patients after receiving allo-HSCT seems to be important not only in AML prognosis but also in therapy efficacy evaluation.

Keywords: acute myeloid leukemia, miR-3151, BAALC, prognosis, allogeneic hematopoietic stem cell transplantation.

Received: October 22, 2018

Accepted: June 7, 2019

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Prognostic Value of Genetic Mutations in Patients with Acute Myeloid Leukemias: Results of a Cooperative Study of Hematology Clinics of Saint Petersburg (Russia) and Charite Clinic (Germany)

EV Motyko1, OV Blau2, LB Polushkina1, LS Martynenko1, MP Bakai1, NYu Tsybakova1, YuS Ruzhenkova1, EV Kleina1, NB Pavlenko1, AM Radzhabova1, EV Karyagina3, OS Uspenskaya4, SV Voloshin1, AV Chechetkin1, IS Martynkevich1

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 Charite Clinic, Berlin Medical University, 30 Hindenburgdamm, Berlin, Germany, 12200

3 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

4 Leningrad Regional Clinical Hospital, 45–49 Lunacharskogo pr-t, Saint Petersburg, Russian Federation, 194291

For correspondence: Ekaterina Vadimovna Motyko, PhD in Biology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)925-05-62; e-mail: genetics.spb@mail.ru

For citation: Motyko EV, Blau OV, Polushkina LB, et al. Prognostic Value of Genetic Mutations in Patients with Acute Myeloid Leukemias: Results of a Cooperative Study of Hematology Clinics of Saint Petersburg (Russia) and Charite Clinic (Germany). Clinical oncohematology. 2019;12(2):211–9.

DOI: 10.21320/2500-2139-2019-12-2-211-219


ABSTRACT

Aim. To analyze the effect on prognosis of mutations that are typical of acute myeloid leukemia (AML) patients.

Materials & Methods. The study included 620 AML patients surveyed at Hematology Clinics of Saint Petersburg (Russia) and Charite Clinic (Berlin, Germany). G-banding of chromosomes was employed for cytogenetic testing. Aberration screening in DNMT3A, IDH1/2 genes was based on real-time polymerase chain reaction (PCR) with subsequent analysis of melting and sequencing profiles. Mutations in FLT3, NPM1 genes were revealed by PCR.

Results. Mutations were identified in 343 (55.3 %) out of 620 patients. Significantly more often mutations were discovered in patients with normal karyotype (NK) (= 0.001). FLT3-ITD mutation was associated with reduced medians of overall survival (OS) and disease-free (DFS) survival: 11.3 vs. 15.8 months with FLT3-ITD– (= 0.005) and 10.0 vs. 13.3 months with FLT3-ITD+ (= 0.009), respectively. The relation of FLT3-ITD allele burden to OS duration was also assessed. In the ITDlow/ITD– group the OS median was considerably longer than in the ITDhigh group (= 0.028). In the group of patients with 1 mutation in NPM1 gene OS and DFS were much better in comparison with other patients (medians of 27.4 and 13.9 months, respectively, = 0.040; 19.3 and 12.0 months, = 0.049). Negative impact of mutations in DNMT3A gene was noticed while assessing OS median: 12 (DNMT3A+) and 15 months (DNMT3A–), respectively (= 0.112). Mutations in IDH1 gene correlated with a better OS than in the group without mutations (= 0.092). The rs11554137 polymorphism in IDH1 gene was associated with worse OS in the group of patients with NK (= 0.186). In 144 patients various mutation combinations (from 2 to 5) were identified. It was demonstrated that mutations in FLT3 (FLT3-ITD), NPM1, DNMT3A, and IDH2 were identified significantly more often in combinations with other mutations (= 0.001): NPM1+/FLT3-ITD+ (20.8 %), NPM1+/FLT3-ITD+/DNMT3A+ (8.3 %), and FLT3-ITD+/DNMT3A+ (8.3 %). Patients with 1 mutation had a noticeably longer OS median compared with patients with 2 mutations (18.1 and 12.2 months; = 0.003). In patients with NPM1+ according to their OS the most unfavorable additional mutation was FLT3-ITD (median 27.4 vs. 9.2 months; = 0.019) and the combination of NPM1+/FLT3-ITD+/DNMT3A+ (median 27.4 vs. 14.6 months; = 0.141). OS of patients with DNMT3A+ showed a downward trend if FLT3-ITD additional mutation was identified (17.3 vs. 7.1 months; = 0.074).

Conclusion. Mutations in FLT3, DNMT3A, IDH1/2, NPM1 genes frequently occur in AML intermediate-risk patients, i.e. they determine the intermediate prognosis group in AML. The studied mutations considerably impact prognosis. It is important to take into consideration mutation type, its allele burden, and the presence of additional mutations. A patient with 2 mutations has a considerably worse OS compared with a patient with 1 mutation. The studied group of patients with the combination of NPM1+/FLT3-ITD+, NPM1+/FLT3-ITD+/DNMT3A+, DNMT3A+/FLT3-ITD+ mutations has the poorest prognosis. Comprehensive analysis of genetic damages in AML patients allows to most accurately predict the course and prognosis of the disease and to plan targeted therapy.

Keywords: acute myeloid leukemias, mutations in FLT3, NPM1, DNMT3A, IDH1/2 genes, karyotype, prognosis.

Received: July 13, 2018

Accepted: January 16, 2019

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Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma

SV Samarina1, EL Nazarova1, NV Minaeva1, EN Zotina1, IV Paramonov1, SV Gritsaev2

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Valer’evna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Nazarova EL, Minaeva NV, et al. Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(1):68–72.

DOI: 10.21320/2500-2139-2019-12-1-68-72


ABSTRACT

Aim. To assess the prognostic value of clinical and hematological parameters used by hematologists for risk stratification in diffuse large B-cell lymphoma (DLBCL), and to justify the need for discovering new prognostic factors.

Methods. The trial included 101 patients (48 men and 53 women) with newly diagnosed DLBCL at the age of 18–80 years (median age 58 years). The patients received R-CHOP as first-line therapy. Depending on their response all patients were stratified into 4 groups: with complete response (CR; n = 58), partial response (PR; n = 15), resistance to first-line therapy (n = 19), and early relapses (ER; n = 9). Median follow-up was 22 months (range 2–120 months).

Results. In terms of age influence on the efficacy of R-СНОР as first-line therapy no significant differences were established in regard to response in patients younger and older than 65 years. Statistically significant differences were observed while analyzing two parameters of International Prognostic Index (IPI; disease stage and extranodal lesions) and B-symptoms in the CR and therapy-resistant groups. With respect to the same parameters no significant differences were found in the CR and ER groups. Median 2-year disease-free survival was not achieved in patients with CR. In patients with PR it was 12 months. Median 2-year overall survival in patients with CR, PR, and ER was not achieved, and in patients with therapy-resistant DLBCL it was 10 months.

Conclusion. Results of the trial confirm prognostic value of factors applied for risk stratification in DLBCL. However, variability of clinical course of the disease, especially with a low IPI score, suggests the need for new prognostic parameters associated with the course of DLBCL.

Keywords: diffuse large B-cell lymphoma, prognosis, induction therapy, survival.

Received: June 5, 2018

Accepted: December 3, 2018

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Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma

AS Luchinin1, SV Semochkin2, NV Minaeva1, NM Pozdeev1, IV Paramonov1

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Aleksandr Sergeevich Luchinin, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS, Semochkin SV, Minaeva NV, et al. Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma. Clinical oncohematology. 2018;11(2):175–81.

DOI: 10.21320/2500-2139-2018-11-2-175-181


ABSTRACT

Aim. To assess prognostic value of surrogate clinical and laboratory markers in current therapy of multiple myeloma (MM).

Materials & Methods. The analysis included 567 patients (215 men and 352 women), the Kirov region inhabitants with newly diagnosed MM over the period from January 1, 1994 to December 31, 2016. The median age was 64 years (range 29–90). Patients were divided into two groups: the first group received treatment from 1994 to 2005 (n = 269), the second group received treatment from 2006 to 2016 (n = 298). Impact of factors on overall survival (OS) was evaluated by multivariate logistic regression analysis using the Cox method.

Results. Over the period from 2006 to 2016 the number of patients treated with traditional chemotherapy decreased from 78.4 to 32.5 %. At the same time the number of patients treated with bortezomib-based regimens increased from 1.9 to 56.3 % and autologous hematopoietic stem cell transplantation (auto-HSCT) protocols — from 1.4 to 14.0 %. Median OS over the period from 1994 to 2005 was 27 months. It increased to 55 months in the period of 2006–2016. In the reference decades 5-year overall survival increased from 21 % (95% confidence interval [95% CI] 17–27 %) to 47 % (95% CI 39–55 %), respectively (hazard ratio [HR] 0.51; 95% CI 0.41–0.64; < 0,0001). In patients treated with bortezomib-based regimens over the period from 2006 to 2016 median OS increased to 73 months compared to 27 months in 1994–2005. In patients aged ≤ 65 years and treated with auto-HSCT median OS was not reached, and median OS in patients without auto-HSCT treatment was 54 months.

Conclusions. Surrogate prognostic markers, such as the age over 65, hemoglobin level < 100 g/L, β2-microglobulin ≥ 6 mg/L, serum creatinine ≥ 177 µmol/L and stage III according to ISS and Durie-Salmon, are unfavourable predictors of survival of MM patients.

Keywords: multiple myeloma, prognosis, bortezomib, auto-HSCT, overall survival.

Received: December 21, 2017

Accepted: February 25, 2018

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REFERENCES

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Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases

VA Misyurin

NN Blokhin National Medical Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Vsevolod Andreevich Misyurin, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(985)436-30-19; e-mail: vsevolod.misyurin@gmail.com

For citation: Misyurin AV. Clinical Significance of the PRAME Gene Expression in Oncohematological Diseases. Clinical oncohematology. 2018;11(1):26–33.

DOI: 10.21320/2500-2139-2018-11-1-26-33


ABSTRACT

Although the PRAME activity was first discovered in solid tumors, this gene is very frequently expressed in oncohematological diseases. PRAME can be regarded as a reliable biomarker of tumor cells. Determination of PRAME transcripts is used in residual disease monitoring and molecular relapse diagnostics. Experimentation with PRAME expressing lines of leukemia cells yielded controversial results. Therefore, it is hardly possible to estimate the prognostic value of PRAME activity in oncohematological diseases. In chronic myeloproliferative disease and chronic myeloid leukemia, however, PRAME activity proves to be a predictor of negative prognosis, and on the contrary, it can be regarded as a positive prognostic factor in acute myeloid or lymphoid leukemia. Despite many clinical studies prognostic value of PRAME expression in some diseases requires further investigation. The present literature review contains the data concerning PRAME expression in oncohematological diseases.

Keywords: PRAME, leukemia, lymphoma, prognosis.

Received: September 14, 2017

Accepted: December 2, 2017

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Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias with Hyperdiploid Karyotype

TL Gindina, NN Mamaev, ES Nikolaeva, SN Bondarenko, OA Slesarchuk, AS Borovkova, SV Razumova, OV Pirogova, AL Alyanskii, LS Zubarovskaya, BV Afanas’ev

RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician IP Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: + 7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Nikolaeva ES, et al. Outcome of Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias with Hyperdiploid Karyotype. Clinical oncohematology. 2016;9(4):383–90 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-383-390


ABSTRACT

Aim. To evaluate the prognostic impact of the different cytogenetic characteristics, including the modal number, the number of chromosomal aberrations in a complex karyotype, and adverse chromosomal abnormalities (ACA) (–7/7q–, –5/5q–, –17/17p–, t(6;9)(p22;q34)) on the results of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with hyperdiploid acute myeloid leukemia (H-AML).

Methods. Forty seven H-AML patients (21 women and 26 men, aged from 1 to 58 years, median — 23.9 years) were examined. The analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed.

Results. The modal number of chromosomes (MN) of 47–48 was the most common one in the karyotype which was observed in 31 (66 %) patients. High hyperdiploidy with the modal number of 49–65 was identified in 13 (28 %) patients, near-triploid and near-tetraploid karyotypes were found in 3 (6 %) patients. Quantitative chromosomal abnormalities were nonrandom. Chromosome 8 (50 %), 21 (32 %), 13 (16 %) и 22 (16 %) trisomy was the most common one. Structural chromosomal abnormalities were detected in 22 (47 %) patients, at that, ACA were found in 7 (19 %) patients. In univariate analysis, the OS and EFS after allo-HSCT differed in patients with different clinical status (remission vs. active disease; = 0.003 and = 0.002, respectively), different chromosomal abnormalities in hyperdiploid karyotype (ACA– vs. ACA+; = 0.001 and = 0.03, respectively). An additional analysis of selected patients group with a structurally complex karyotype (n = 19) showed, that patients without ACA had a higher OS than patients with ACA (= 0.03). In multivariate analysis, the disease status (relapse) at allo-HSCT was an independent predictor of decreased OS and EFS (= 0.004 и = 0.006, respectively), as well as the presence of the ACA (= 0.002 only for OS).

Conclusion. ACA were high-risk factors in H-AML patients received allo-HSCT. Therefore, the patients with formal criteria of a complex karyotype should not be automatically included in the cytogenetic unfavorable risk group.


Keywords: hyperdiploid and complex karyotypes, acute myeloid leukemia, allogeneic hematopoietic stem cell transplantation, prognosis.

Received: April 17, 2016

Accepted: May 5, 2016

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REFERENCES

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Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities

TL Gindina, NN Mamaev, SN Bondarenko, ES Nikolaeva, IA Petrova, OA Slesarchuk, AS Borovkova, SV Razumova, AL Alyanskii, LS Zubarovskaya, BV Afanas’ev

R.M. Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Academician I.P. Pavlov First St. Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel.: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Gindina TL, Mamaev NN, Bondarenko SN, et al. Allogeneic Hematopoietic Stem Cell Transplantation in Acute Myeloid Leukemias: Prognostic Significance of Complex Karyotype Including del(5q), –7, del(7q) Abnormalities. Clinical oncohematology. 2016;9(3):271-78(In Russ).

DOI: 10.21320/2500-2139-2016-9-3-271-278


ABSTRACT

Aim. To evaluate the prognostic significance of the complex karyotype including del(5q), –7, del(7q) abnormalities in acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Materials & Methods. Forty-four AML patients with chromosome 5 and/or 7 abnormalities (22 women and 22 men, aged from 1.2 to 67 years, median 31.2 years) were examined. Analysis of overall (OS) and event-free survival (EFS) predictors after allo-HSCT in patients with different clinical, transplant and cytogenetic characteristics was performed.

Results. Prior to allo-HSCT, the complex karyotype (with three or more chromosomal abnormalities) was observed in 19 (43 %) patients, the monosomal karyotype was in 8 (18 %) patients. Univariate analysis demonstrated that OS and EFS differed in patients from different age groups (³ 18 vs. < 18 years; = 0.01 and = 0.05, respectively), with different disease status at transplantation (1 remission vs. other clinical status; = 0.1 and = 0.008, respectively), with and without complex karyotype (СK– vs. CK+; = 0.05 and = 0.002, respectively), with and without monosomal karyotype (МK– vs. MK+; = 0.009, only for EFS), and with different stem cells source (bone marrow vs. other source; = 0.03 only for OS). Multivariate analysis confirmed that age of 18 years and more (= 0.02 and = 0.01, respectively), active disease at allo-HSCT (= 0.04 and = 0.005, respectively), complex karyotype (= 0.04 и = 0.0008, respectively) and stem cell source other than bone marrow (= 0.02 only for OS) were independent predictors of OS and EFS deterioration.

Conclusion. The study demonstrates that chromosome 5 and/or 7 abnormalities as a part of the complex karyotype is high-risk factor in AML patients undergoing allo-HSCT (unlike the monosomal karyotype), that requires the special therapeutic approach.


Keywords: acute myeloid leukemias, complex karyotype, chromosome 5 and 7 abnormalities, allogeneic hematopoietic stem cell transplantation, prognosis.

Received: March 5, 2016

Accepted: April 5, 2016

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REFERENCES

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Genetic Mutations in Acute Myeloid Leukemia

OV Blau

Charite Clinic, Berlin Medical University, 30 Hindenburgdamm, Berlin, Germany, 12200

For correspondence: Ol’ga Vladimirovna Blau, DSci, Department of Hematology, Oncology and Tumorimmunology, Charite University School of Medicine, Hindenburgdamm 30, 12200, Berlin, Germany; e-mail: olga.blau@charite.de.

For citation: Blau OV. Genetic Mutations in Acute Myeloid Leukemia. Clinical oncohematology. 2016;9(3):245-56 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-245-256


ABSTRACT

Acute myeloid leukemia (AML) is a clonal malignancy characterized by ineffective hematopoiesis. Most AML patients present different cytogenetic and molecular defects associated with certain biologic and clinical features of the disease. Approximately 50–60 % of de novo AML and 80–95 % of secondary AML patients demonstrate chromosomal aberrations. Structural chromosomal aberrations are the most common cytogenetic abnormalities in about of 40 % of de novo AML patients. A relatively large group of intermediate risk patients with cytogenetically normal (CN) AML demonstrates a variety of outcomes. Current AML prognostic classifications include only some mutations with known prognostic value, namely NPM1, FLT3 and C/EBPa. Patients with NPM1 mutation, but without FLT3-ITD or C/EBPa mutations have a favorable prognosis, whereas patients with FLT3-ITD mutation have a poor prognosis. A new class of mutations affecting genes responsible for epigenetic mechanisms of genome regulations, namely for DNA methylation and histone modification, was found recently. Among them, mutations in genes DNMT3A, IDH1/2, TET2 and some others are the most well-studied mutations to date. A number of studies demonstrated an unfavorable prognostic effect of the DNMT3A mutation in AML. The prognostic significance of the IDH1/2 gene is still unclear. The prognosis is affected by a number of biological factors, including those associated with cytogenetic aberrations and other mutations, especially FLT3 and NPM1. The number of studies of genetic mutations in AML keeps growing. The data on genetic aberrations in AML obtained to date confirm their role in the onset and development of the disease.


Keywords: acute myeloid leukemia, AML, karyotype, cytogenetic aberrations, gene mutation, prognosis.

Received: January 23, 2016

Accepted: April 4, 2016

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Association between HLA-DRB1 alleles and response to imatinib in chronic myeloid leukemia

E.G. Ovsyannikova1, I.L. Davydkin2, E.A. Popov1, L.V. Zaklyakova1, and B.N. Levitan1

1 Astrakhan State Medical Academy, RF Ministry of Health, Astrakhan, Russian Federation

2 Research Institute of Hematology, Transfusiology, and Intensive Care, Samara State Medical University, RF Ministry of Health, Samara, Russian Federation


ABSTRACT

The article presents analysis of association between the HLA-DRB1 gene alleles and the response to imatinib in the patients with Ph-positive chronic myeloid leukemia (Ph+ CML). HLA class II alleles, DRB1 locus, were determined using PCR-SSP. The predictors of optimal response to imatinib in 3 to 18-months treatment of CML are HLA-DRB1*16(02), HLA-DRB1*17(03), and HLA-DRB1*08 specificities. Immunogenetic markers of imatinib treatment failure are HLA-DRB1*11(05), HLA-DRB1*12(05), and HLA-DRB1*14(06) alleles. The results obtained can be used for the development of individual long-term prognosis for chronic myeloid leukemia and optimization of the treatment choice.


Keywords: chronic myeloid leukemia, HLA-DRB1, imatinib, prognosis.

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