Clinical efficiency of Dacogen (inhibitor of DNA hypermethylation) in 16 patients with MDS is presented. Bone marrow cytogenetic studies were performed in 6 patients; the detected chromosome aberrations included 5q deletion in 1 patient, X monosomy in 2 and multiple clonal rearrangements in 1. Results of this study indicated that after 4 courses of Dacogen (15mg/m2 i.v. 3 times daily for 3 days each course) significant clinical and hematological effects is received (according to standard criteria [1]): a complete response was in 3 patients; no partial response was registered; stabilization and bone marrow remission were achieved in 1 and 4 patients respectively. Response duration was 3.5 months. Drug myelotoxicity which would influence on intercourse interval and cause dose reduction during treatment was not revealed.

The expression of retinoic acid nuclear receptor gene RARα and its relationship with expression of APE1, YB-1, and MDR1 genes was studied in bone marrow aspiration biopsy specimens from 22 patients with newly detected multiple myeloma. The expression of RARα directly correlated with the expression of APE1/YB-1/MDR1 pattern genes. Groups differing by expression of RARα exhibited significant differences in the overall survival of patients; concordant and simultaneous changes in the expression of all genes of the APE1/YB-1/MDR1 pattern suggested the level of RARα gene expression as a potential prognostic factor in the pathogenesis of multiple myeloma.

Introduction:The RARa is a transcription factor playing important role in such processes as proliferation, differentiation and apoptosis of cells in norm and in tumor. At the same time, it is little known about significance of expression of two major products of transcription of gene RARa - isoforms RARa and RARa - in pathogenesis of solid and non-solid tumors, including multiple myeloma. The actual data testify ambiguity of input made by isoforms RARa and RARa into processes of tumor development and progression of malignant tumors.The results:It was established that higher level of expression of isoform RARa in combination with increased expression of isoform RARβ (group 1) statistically reliable associated with lesser decreasing of concentration of Bence Jones protein in urine of patients in the result of applied treatment and, therefore, lesser effectiveness of response to standard treatment according protocol M-2 in comparison with group II which included patients with lesser levels of expression of RARa and RARβ (32.8% and 62.8% for groups I and II correspondingly; p=0.037). The analysis of indices of survival of examined patients in groups I and II demonstrated that median of total survival of patients from group I was reliably lower than in patients included into group II (30 and 84 correspondingly; p=0.046).Conclusion:The results of study demonstrate that increased level of expression in the first instance of isoform RARa in combination with hyper-expression of isoform RARβ but not RARa can have unfavorable significance in case of evaluation of response to medicinal therapy and prognosis of total survival in patients with multiple melanoma.

The significance of quantitative changes of ALDH1A1 and RDH10 gene expression in 22 non-treated multiple myeloma patients were studied. We found a direct correlation between the expression of ALDH1A1 and RDH10 genes. We showed that ALDHA1 and RDH10 expression were inversely related with expression of a key gene for all-trans-retinoic acid catabolism, CYP26A1, and correlated with expression of RARα and PPARβ/ genes. In addition for the first time it was re- vealed that increased expression of ALDH1A1-RDH10-RARα- PPARβ/δ pattern could be considered as adverse prognostic factor associated with a higher concentration of paraprotein and worst overall survival of patients with newly diagnosed multiple myeloma.

In this study, for the first time the expression of β₂ and β₄ isoforms of RARβ gene was investigated in group of 19 patients with the newly diagnosed multiple myeloma. The expression of both RARβ₂ and RARβ₄ isoforms was detected in all patients, but it was different and had opposite tendency. We showed that RARβ₄ expression level positively correlated with VEGF-A and VEGFR1 expression levels. It was found that higher levels of RARβ₄/VEGF-A/VEGFR1 co-expression were defined of patients with statistically significant increase of plasma cell level and paraprotein concentration. The median overall survival was lower in patients with RARβ₄, over-expression, while the maximal median overall survival was observed of patients with RARβ₂ down-regulation and nearly absolute RARβ₄inactivation.

In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL) are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.

Imatinib (IM) treatment efficacy in 116 chronic myeloid leukemia (CML) patients in different studies was analyzed. Patient group was non‑selective with prospective enrollment. The study was based on real‑time patient’s register allows to treatment quality control due to clinical results. Cytogenetic response (CO), hematological data, and overall survival (OS) were used as criteria for the therapy efficacy. After 12 month of treatment in 46.4 % of CML patients in early chronic phase complete CO (CCO) was obtained, in 33.3 % — in the late chronic phase, and in 13.3 % — in accelerated phase. Deficit of daily imatinib dose and intervals in treatment schedule were made a negative influence on CO quality. The median of OS was 120 months.

This study aimed to evaluate treatment results in patients with diffuse large cell lymphoma (DBL CL) received R-CHOP program (as 1 st and2 nd line therapy), including cases with complications. We observed 77 DBLCL patients (50 primary and 27 received other chemotherapy programs, in relapse, progression or treatment resistance phase). The median age is 54.1 years (21–79 years). 33 patients (43 %) had a high risk for unfavorable disease course according to IPI. Complications associated with development of severe compression syndromes, which required the appropriate surgical intervention, w as diagnosed in 45 (58.4 %) patients. From 50 primary patients received R-C HOP as the f irst line therapy objective treatment response was registered in 47 (94.0 %). Complete response was registered in 43 (86.0 %). The proportion of patients in whom response was maintained for 6 months w as 72.0 % in group with maintenance therapy and 28.0 % in group without it. These results were achieved when induction period density was 0.9. The last parameter is the ratio of the courses number to their time in mon ths. The density of standard induction R-C HOP-21 is 1.4. From 27 relapse or refractory patients received R-C HOP as the second line therapy objectivetreatment response was registered in 85.1 % of patients. Induction period density w as 1.03. The proportion of patients in whom response was maintained for 6 months was 74.0 %. Three classes serum Ig concentrations analysis before and after induction period in 16 pati ents showed normal values. With the median (Me) follow-up time in all patients over 24 months 3-years survival w as 93 % and Me w as not achieved. 3-years survival was 100 % in primary patients and 80 % in patients with previously treatment, and Me is also not achieved.

AIM:To determine the significance of the angiogenic activity estimated from the gene expression of the vascular endothelial growth factors (VEGFs) VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFR1, VEGFRls, VEGFR2, and VEGFR3 in the mononuclear cell fraction of bone marrow (BM) aspirates with tumor plasma cells predominating in different variants of the course of multiple myeloma (MM). MATERIALS AND METHODS:The gene expression of VEGF-A, VEGF-C, and VEGF-D and their receptors VEGFRI, VEGFRls, VEGFR2, and VEGFR3 was determined by reverse-transcription polymerase chain reaction (RT-PCR). RESULTS:VEGF-A, VEGF-C, VEGF-D, as well as VEGFR1, VEGFRls, VEGFR2, and VEGFR3 were expressed showing different intensities in the mononuclear cell fraction of BM aspirates with a predominance of tumor plasma cells in the patients with MM, which allowed patient groups to be identified. In the group of high gene expression of VEGFs and their receptors, the number of clusters of plasma cells and vascular endothelium in the BM aspirates and the degree of osteolysis in the skeletal bones of patients with MM were significantly higher than those in the group of low or absent gene expression. The survival in the latter group was significantly higher. CONCLUSION:The investigation could provide an estimate of angiogenic processes in MM and establish their association with clinical manifestations and cytological characteristics.

Imatinib (IM) treatment efficacy in 116 chronic myeloid leukemia (CML) patients in different studies was analyzed. Patient group was non‑selective with prospective enrollment. The study was based on real‑time patient’s register allows to treatment quality control due to clinical results. Cytogenetic response (CO), hematological data, and overall survival (OS) were used as criteria for the therapy efficacy. After 12 month of treatment in 46.4 % of CML patients in early chronic phase complete CO (CCO) was obtained, in 33.3 % — in the late chronic phase, and in 13.3 % — in accelerated phase. Deficit of daily imatinib dose and intervals in treatment schedule were made a negative influence on CO quality. The median of OS was 120 months.

The efficiency of bortezomib protocols is evaluated in 27 patients with multiple myeloma and renal failure. The mean serum creatinine level in those patients was 642 +/- 55 mmol/liter, glomerular filtration 14.9 +/- 1.3 ml/min. Combined therapy by bortezomib protocols and hemodyalisis was carried out in 14 patients, 13 patients received cytostatic therapy alone. Antitumor response, recovery of renal function parameters, and overall survival were evaluated. Patients receiving antitumor bortezomib therapy in combination with hemodialysis exhibited an objective antitumor response of 63.3%, with substitute renal therapy of 1 to 42 months (median 6 months). Renal function values improved significantly after 6 months of treatment. The need in hemodialysis persisted in 8 (57.2%) patients, in 2 (14.3%) patients hemodialysis had to be resumed after its discontinuation, and no more hemodialysis was needed in 4 (28.5%) patients. The objective response in patients receiving only antitumor bortezomib therapy was virtually the same as in hemodialysis subgroup -61.5%. Renal function improved as well. Survival median in the subgroups was 50 and 48 months, respectively. The study has demonstrated high efficiency of bortezomib protocols for the treatment of patients with multiple myeloma complicated by renal failure. Antitumor therapy was supplemented by hemodialysis in patients with glomerular filtration below 20 ml/min.