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Introduction Acute myeloid leukemia (AML) is an infrequent (1.3%), highly malignant neoplasm responsible for a large number of cancer-related deaths [ 1 , 2 ]. In the USA and other highly developed countries, the incidence has been near stable over the last years and is about 4 cases per 100,000 citizens per year [ 1 , 2 , 3 ]. The median age at diagnosis is 67 years [ 1 , 2 , 3 ]. AML is a heterogeneous and complex disease in which genomic and proteomic alterations and the interactions between them result in various apoptosis abnormalities [ 1 , 2 , 3

, Lu JY, Li M, Du P, Xu GL, et al. Growth of G422 glioma implanted in the mouse brain was affected by the immune ability of the host. Chin Med J (Engl). 2011;124(13):1994-8. 13. Ma YH, Yu JB, Yao HP, Zhan RY, Zheng JS. Treatment of intracerebral glioblastomas with G422 tumour cell vaccine in a mouse model. J Int Med Res. 2008;36(2):308-13. 14. Wang H, Tu HJ, Qin J, Li XJ, Huang KM, Zhou ZM, et al. [Effect of cryotherapy and 5-fluorouracil on apoptosis of G422 glioma cells]. Ai Zheng. 2004;23(4):412-5. 15. Li F, Cheng Y, Lu J, Hu R, Wan Q, Feng H. Photodynamic therapy

apoptosis via Bak/Bax if Mcl-1 is neutralized. Cancer Cell 2006;10:389-99. Vandenberg CJ Chen L Czabotar PE et al The BH3 mimetic ABT-737 targets selective Bcl-2 proteins and efficiently induces apoptosis via Bak/Bax if Mcl-1 is neutralized Cancer Cell 2006 10 389 99 [9] Scheffold A, Jebaraj BMC, Stilgenbauer S. Venetoclax: Targeting BCL2 in Hematological Cancers. Recent Results Cancer Res 2018;212:215-42. Scheffold A Jebaraj BMC Stilgenbauer S Venetoclax: Targeting BCL2 in Hematological Cancers Recent Results Cancer Res 2018 212 215 42 [10] Korycka-Wołowiec A, Wołowiec D

), interleukin 6 and 8 (IL-6, IL-8), [ 8 , 16 , 17 , 18 ,]. VEGF stimulates the formation of new blood vessels and increases vascular permeability [ 8 ]. This cytokine promotes EC survival by lowering their susceptibility to apoptosis [ 19 ]. VEGF activates phosphatidylinositol-3-kinase/ protein kinase B (PI3K/Akt) pathway and reduces the pro-apoptotic potency of chemotherapy [ 8 , 19 ]. It has been shown that VEGF significantly influences the immune system, and inhibits differentiation, and maturation of dendritic cells (DC). It results in decreased expression of major

, .: Molecular mechanisms regulating the vascular prostacyclin pathways and their adaptation during pregnancy and in the newborn. Pharmacological Reviews, 2012 8. Slomp J., et al.: Differentiation, dedifferentiation, and apoptosis of smooth muscle cells during the development of the human ductus arteriosus. Arterioscler Thromb Vasc Biol, 1997. 17(5): 1003-9 9. Hong Z., et al.: Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus. Circ Res, 2013, 112 (5): 802-15 10. Obladen M.: History of the ductus

blocking the cell cycle at the G1 phase [ 28 ]. Current published HDACis include valproic acid (VPA), vorinostat, entinostat, and panobinostat. VPA, a short-chained fatty acid, was demonstrated to promote growth inhibition, apoptosis induction, and reactivation of p57KIP2 and p21CIP1 in leukemic cell lines HL-60 and MOLT4 when combined with DAC [ 29 ]. However, in vivo , the combination regimen did not show antileukemia activity. A phase 1/2 and a phase 1 study revealed that the addition of VPA led to neurotoxicity, whose severity depended on the dose [ 30 , 31 ]. A

lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial Blood 2009 114 13 2589 – 97 [12] Turgut B, Vural O, Pala FS, et al. 17p Deletion is associated with resistance of B-cell chronic lymphocytic leukemia cells to in vitro fludarabine-induced apoptosis. Leuk Lymphoma 2007;48(2):311–20. Turgut B Vural O Pala FS et al 17p Deletion is associated with resistance of B-cell chronic lymphocytic leukemia cells to in vitro fludarabine-induced apoptosis Leuk Lymphoma 2007 48 2 311 – 20

. Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells. Vitr Cell Dev Biol Anim 2017;53:841–51. Tachikawa S Nishimura T Nakauchi H Ohnuma K Thalidomide induces apoptosis in undifferentiated human induced pluripotent stem cells Vitr Cell Dev Biol Anim 2017 53 841 51 [28] Gardner R V, McKinnon E, Astle CM. Analysis of the stem cell sparing properties of cyclophosphamide. Eur J Haematol 2001;67:14–22. Gardner R V McKinnon E Astle CM Analysis of the stem cell sparing properties of cyclophosphamide Eur J Haematol 2001 67 14 22 [29] DiPersio JF

) for experiments involving humans; EU Directive 2010/63/EU for animal experiments; Uniform Requirements for manuscripts submitted to biomedical journals. References/Piśmiennictwo [1] Kipps TJ, Stevenson FK, Wu CJ, et al. Chronic lymphocytic leukaemia. Nat Rev Dis Primers 2017;3:16096. Kipps TJ Stevenson FK Wu CJ et al Chronic lymphocytic leukaemia Nat Rev Dis Primers 2017 3 16096 [2] Podhorecka M, Macheta A, Bozko M, et al. Deregulation of apoptosis – Is it still an important issue in pathogenesis of chronic lymphocytic leukemia? Curr Cancer Drug Targets 2016

immunomodulatory drugs [ 8 , 9 ], e.g., by cyclosporin A withdrawal, which is thought to be attributable to self-reactive CD8+ T-cells escaping apoptosis. It can affect only a single organ (e.g., skin or gastrointestinal tract) or may present with multiorgan involvements [ 1 , 7 , 10 , 11 , 12 , 13 , 14 , 15 ]. The differential diagnosis of auto-GVHD is difficult and requires the exclusion of other probable causes of the reported abnormalities. Although this pathology may easily be confused with other conditions, it is potentially curable if promptly and correctly