[Aberrant methylation of the promoter regions of the SOX7 and p15INK4b genes and Wnt signaling pathway antagonists in patients with acute myeloid leukemias]. / Aberrantnoe metilirovanie promotornykh oblastei genov SOX7, p15INK4b i antagonistov signal'nogo puti Wnt u bol'nykh ostrymi mieloidnymi leikozami.

AIM: to investigate the methylation status of the SOX7 and p15NK4b genes and Wnt signaling pathway antagonists in patients with acute myeloid leukemia (AML) in order to assess the association of the rate of aberrant methylation (AM) with the morphological variant and pattern of chromosomal aberrations, as well as the impact of the methylation status on survival. SUBJECTS AND METHODS: The data of 57 AML patients aged 20 to 79 years were analyzed. The methylation status of the genes was studied by methylation-specific polymerase chain reaction. RESULTS: The signs of the AM of ≥1 gene were detected in 52 (91.2%) of the 57 patients. The most common finding was AM of simultaneously 2 or 3 genes: in 29.8 and 21.1% of the patients, respectively. Concurrent methylation of 3-5 genes proved to be a more frequent finding in AML patients with myelodysplasia: in 7 (70%) of 10 patients. The proportion of patients with methylation of 5 genes was considerably higher in a group of patients with a complex karyotype: 50% versus 8.3% among other patients (odds ratio: 11.0; 95% confidence interval 2.0 to 61.6; p=0.01). There were no differences in the median overall and relapse-free survival rates in patients with a normal karyotype and without FLT3 and NPM mutations, who received induction therapy, in relation to the number of genes with AM. CONCLUSION: AM of the p15NK4b and SOX7 genes and Wnt signaling pathway antagonists is detected in the majority of patients with AML, which allows hypomethylating agents to be recommended for the treatment of patients who cannot use intensive cytostatic therapy for different reasons. The detection of a large number of genes with the aberrant methylation status in most AML patients with myelodysplasia or a complex karyotype serves as the basis for initiating trials to evaluate the efficiency of a combination of 5-azacytidine and cytostatics.

[Transformation of secondary myelodysplastic syndrome to atypical chronic myeloid leukemia in a female patient with acute myeloid leukemia]. / Transformatsiya vtorichnogo mielodisplasticheskogo sindroma v atipichnyi khronicheskii mieloleikoz u bol'noi ostrym mieloidnym leikozom.

Secondary myeloid neoplasia may be a complication of intensive cytostatic therapy. The most common types of secondary neoplasias are acute myeloid leukemia and myelodysplastic syndrome. The development of secondary atypical chronic myeloid leukemia (aCML) is an extremely rare phenomenon. The paper describes transformation of secondary myelodysplastic syndrome to aCML 6 months after its diagnosis. The development of aCML was accompanied by additional chromosomal aberration as monosomy of chromosome 17. No mutations in the JAK2, MPL, and CalR genes were detected. It is concluded that the clinical course of secondary myeloid neoplasias is variable.

[The specific features of diagnosis of mixed-phenotype acute leukemia: A combination of B-cell antigen expressions according to the results of flow cytometry and morphological markers of myeloid differentiation in blast cells: A clinical case].

This rare type of acute leukemia, blast cells of which express myeloid and/or lymphoid markers, is mainly diagnosed using flow cytometric findings. The paper describes a clinical case of mixed-phenotype acute leukemia, in which B-cell lymphoid antigen expressions were revealed by a flow cytometric technique, while bone marrow morphological specimens showed the signs of myeloid differentiation specific to blast cells. It is concluded that there is a need for a comprehensive examination of patients with new-onset acute leukemia and for an aggregate analysis of flow cytometric results with morphological and cytochemical findings.

[The specific features of the immunophenotype of blast cells in patients with de novo normal karyotype acute myeloid leukemia and FLT3-ITD mutation].

AIM: To study the specific features of de novo acute myeloid leukemia (AML) with FLT3-ITD mutation. SUBJECTS AND METHODS: The results of examination were analyzed in 101 patients. Bone marrow morphological specimens were stained with Pappenheim stain. The karyotype was investigated using the standard GTG-banding method. Blast cells were immunotyped in a five-color analysis on a Cytomics FC 500 laser flow cytofluorometer. RESULTS: FLT3-ITD mutation was identified in 21 patients who had a varying morphological nature of blasts, different karyotype variants, and frequently additional NPM1 gene mutation. The distinctive property of 10 patients with normal karyotype and FLT3-ITD mutation (without NPM1 gene mutation) was the larger number of cases with high expression of HLA-DR and CD7 than in the control group that included 18 patients with normal karyotype AML without FLT3-ITD nutation: 50% versus 6.2% (p = 0.007) and 100% versus 55.6% (p = 0.014), respectively. CONCLUSION: Normal karyotype AML with FLT3-ITD mutation is a group that is homogeneous in the biological phenotype of leukemia cells.

[The efficacy of polychromatic visible and infrared radiation used for the postoperative immunological rehabilitation of patients with breast cancer].

The immunological rehabilitation of the patients with oncological problems after the completion of standard anti-tumour therapy remains a topical problem in modern medicine. The up-to-date phototherapeutic methods find the increasingly wider application for the treatment of such patients including the use of monochromatic visible (VIS) and near infrared (nIR) radiation emitted from lasers and photodiodes. The objective of the present study was to substantiate the expediency of postoperative immune rehabilitation of the patients with breast cancer (BC) by means of irradiation of the body surface with polychromatic visible (pVIS) in combination with polychromatic infrared (pIR) light similar to the natural solar radiation without its minor UV component. The study included 19 patients with stage I--II BC at the mean age of 54.0 +/- 4.28 years having the infiltrative-ductal form of the tumour who had undergone mastectomy. These patients were randomly allocated to two groups, one given the standard course of postoperative rehabilitation (control), the other (study group) additionally treated with pVIS + pIR radiation applied to the lumbar-sacral region from days 1 to 7 after surgery. A Bioptron-2 phototherapeutic device, Switzerland, was used for the purpose (480-3400 nm, 40 mW/cm2, 12 J/cm2, with the light spot diameter of 15 cm). The modern standard immunological methods were employed. It was found that mastectomy induced changes of many characteristics of cellular and humoral immunity; many of them in different patients were oppositely directed. These changes were apparent within the first 7 days postoperatively. The course of phototherapy (PT) was shown to prevent the postoperative decrease in the counts of monocytes and natural killer (NK) cells, the total amount of CD3+ -T-lymphocytes (LPC), CD4+ -T-helpers, activated T-lymphocytes (CD3+ HLA-DR+ cells) and IgA levels as well as intracellular digestion rate of neutrophil-phagocyted bacteria. Moreover PT promoted faster normalization of postoperative leukocytosis and activation of cytotoxic CD8+ -T-LPC, reduced the elevated concentration of immune complexes in blood. Among the six tested cytokines, viz. IL-1beta, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma, only the latter two underwent significant elevation of their blood concentrations (IL-6 within 1 day) and IFN-gamma (within 7 days after mastectomy). The course of PT resulted in the decrease of their levels to the initial values. The follow-up of the treated patients during 4 years revealed neither recurrence of the disease nor the appearance of metastases.