Hypocholesterolemia, an unfavorable feature of prognostic value in chronic myeloid leukemia

Abstract

In chronic myeloid leukemia (CML) low serum cholesterol is not uncommon and has been linked to the activity of the disease. Despite these observations, most studies concerned with prognostic signs in CML have not included cholesterol. In our study, cholesterol correlated positively with survival (p = 0.0012) and with the duration of chronic phase (p = 0.0059) in a univariate analysis. The multivariate Cox regression model selected cholesterol as a parameter of additive prognostic value in addition to marrow myeloblasts plus promyelocytes, sex, eosinophilia and lactate dehydrogenase.

Period prevalence and mortality rates associated with hypocholesterolaemia in dogs and cats: 1,375 cases

“…The relationship of hypocholesterolaemia with death in humans is well established and a similar linear trend to our study was also demonstrated in three human hospitals (Windler et al 1994, Bonville et al 2004. Hypocholesterolaemia is not only acknowledged to have a strong prognostic significance in human critical illness and acute disease (Gui et al 1996, Gordon et al 2001, Dunham et al 2003, Bonville et al 2004, Barlage et al 2009, Lagrost et al 2014, Yamano et al 2016, but also in chronic disease processes such as chronic kidney disease (Iseki et al 2002, Tsirpanlis et al 2009, neoplasia (Muller et al 1989, Sok et al 2009 and liver cirrhosis (Janičko et al 2013). The findings in our study provide further evidence in veterinary medicine to support cholesterol as a prognostic marker for non-survival in a broad small animal population and not just in critical illness.…”

The BCR-ABL1 Inhibitors Imatinib and Ponatinib Decrease Plasma Cholesterol and Atherosclerosis, and Nilotinib and Ponatinib Activate Coagulation in a Translational Mouse Model

“…First, there is, inherent to the diagnosis and progression of the disease, a shortage of suitable high quality plasma samples of CML patients collected at both baseline and follow-up under similar conditions. Second, CML affects both metabolic ( 10 ) and coagulation ( 11 ) parameters which makes it difficult to elucidate the role of TKI treatment on the reported VAEs independently of the underlying disease. Last, we were able to investigate a broad range of parameters, including atherosclerosis and gene expression and pathway analysis of the liver, which is not possible in CML-patients.…”

“…However, it is still unclear whether the side effects are caused by enhanced vascular inflammation and endothelial dysfunction, atherosclerosis development, increased thrombotic activity per se , or a combination of these processes. Furthermore, the underlying disease has been reported to affect metabolic parameters ( 10 ) and coagulation ( 11 ), which may interfere with the onset of the side-effects upon treatment. Therefore, to elucidate the role of TKI treatment on VAE’s independently of a background of leukemia, we performed a detailed experimental study in healthy pro-atherogenic mice.…”

Hypocholesterolemia

“…Several cancers have been associated with low levels of TC, LDL-C and triglycerides (TG) (gastrointestinal cancers [22], lung cancer [23], hepatocellular carcinoma [24], breast cancer [25], hematological malignancies [26][27][28][29][30][31], head and neck cancer [32], adrenal adenoma [33] and pancreatic islet tumors [34]). Regarding hematologic malignancies, acute myelogenous leukaemia [35], hairy cell leukaemia [26], chronic myeloid leukaemia [28], paraproteinemias and lymphomas [27,29] have all been linked to hypolipoproteinemia. Multiple myeloma (particularly in stages II and III) and several other paraproteinemias have been associated with hypocholesterolemia [29], although hypercholesterolemia has also been described [31].…”