Malignant cells are characterized by an increased content of endogenous formaldehyde formed as a by‐product of biosynthetic processes. Accumulation of formaldehyde in cancer cells is combined with activation of the processes of cellular formaldehyde clearance. These mechanisms include increased ALDH and suppressed ADH5/FDH activity, which oncologists consider poor and favorable prognostic markers, respectively. Here, the sources and regulation of formaldehyde metabolism in cancer cells are reviewed. The authors also analyze the participation of oncoproteins such as fibulins, FGFR1, HER2/neu, FBI‐1, and MUC1‐C in the control of genes related to formaldehyde metabolism, suggesting the existence of two mutually exclusive processes in cancer cells: 1) production and 2) oxidation and elimination of formaldehyde from the cell. The authors hypothesize that the study of the anticancer properties of disulfiram and alpha lipoic acid – which affect the balance of formaldehyde in the body – may serve as the basis of future anticancer therapy.
Over the past decades, there has been a significant expansion of the treatment options for patients with chronic lymphocytic leukemia (CLL) due to Brutons tyrosine kinase (BTK) inhibitors, which changed approaches in CLL therapy. Ibrutinib was the first BTK inhibitor approved for CLL treatment, but adverse events such as atrial fibrillation and hypertension may limit the use of ibrutinib. In the first head-to-head trial of acalabrutinib and ibrutinib ELEVATE-RR, acalabrutinib was statistically superior to ibrutinib in all-grade atrial fibrillation/flutter (9.4% vs 16.0%; р=0.023). In all-grade arterial hypertension (9.4% vs 23.2%) and grade 3 (4.1% vs 9.1%) acalabrutinib was statistically superior to ibrutinib. Acalabrutinib demonstrated fewer discontinuations due to adverse events (14.7%) vs ibrutinib (21.3%). Based on ELEVATE-RR results acalabrutinib should be considered as a drug of choice among BTK inhibitors for CLL patients, including patients with cardiovascular diseases and risks of cardiovascular diseases.
Background: Modern therapy diminished prognostic significance of serum β2M level. Aims: This study was designed to investigate the correlation between the number of lymphocytes expressing β2M, serum β2M level, and the results of treatment. Methods: 45 patients (pts) were included (Binet stage B, 36 and C, 9). β2M expression on the lymphocyte surface was detected with immunocytochemical method by means of Dako-Cytomation LSAB2 System HRP, β2M serum level by ELISA. Results: In 29 pts β2M was expressed on 80–100% of lymphocytes (group I), in 16 pts on 35–79% (group II). Number of lymphocytes expressing β2M did not correlate with lumphocyte dimension, form of nucleus, and presence of prolymphocytes in peripheral blood (PB). β2M serum level ranged from 3,0 to 10,5 mg/L. Number of leukocytes and lymphocytes in PB and bone marrow in both groups had no difference. Number of pts with normal β2M serum level (3,5 mg/L or less) was practically the same (group I, 13,8%; group II, 18,8%). Among pts with high β2M serum level (> 6 mg/L) there were 28% in group I and 69,0% in group II. Increased level of LDG (>450 MU/L) was detected in 10% of pts of group I and in 50% in group II. Treatment in both groups was similar: regimens with fludarabine–gr.I, 23 of 29 pts and gr.II, 12 of 16; R-COP–gr.I, 3 pts and gr.II, 2 pts. Two pts in gr.II received leukeran; 3 pts in gr.I didn’t need any treatment. Of 42 pts treated 20 pts achieved complete remission; 13, partial remission, and 9 pts failed. In gr.I complete remission was achieved in 17 of 26 treated pts (65,4%), in gr.II, in 3 of 16 (18,8%), p=0,0038. Partial remission was received in 6 pts of gr.I (23,1%) and in 7 pts (43,8%) of gr.II, p=0,14. Three pts of gr.I (11,5%) and 6 pts of gr.II (37,2%) failed (p=0,05). Conclusion: Comparison of the therapy results showed that β2M expression on large number (80–100%) of lymphocytes in B-CLL can be considered as the favourable prognostic sign. It was associated with lower level (<6 mg/L) of serum β2M (in 71,2% vs. 31% of pts, p=0,009) and LDG (90% vs. 50% of pts, p=0,0051). Disclosure: No relevant conflicts of interest to declare.
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