**4. Is the metabolic syndrome a risk factor for some malignant hemopathies?**

The main risk factors for excess weight and obesity are high caloric diet and sedentary lifestyle. A study conducted in a county hospital in Transylvania examined the presence of MS in all 56 patients with NHL existing in its records and a control group of 64 consecutive patients with non-cancerous diseases in the same hospital (control group). Patients with NHL had significantly more frequently arterial hypertension, significantly higher body mass index values, and a significantly higher number of components of the MS as compared to those of the control group. This observation advocates the idea that excess weight may be a risk factor for this type of neoplasia. (Mihăilă et al., 2009)

In a group of 170 non-Hispanic white pediatric cancer survivors, among males, body adiposity was more important in survivors than in witnesses, as was trunk fat. The survivors had higher values of CH, TG, LDL-cholesterol than the witnesses, and the first watched TV more hours than controls (Miller TL et al., 2010). It was observed that the young survivors of ALL, disease which they had in their childhood, especially those who received cranial radiotherapy, are likely to develop hyperlipidemia, insulin resistance, obesity, arterial hypertension and even MS soon after the treatment (Trimis et al., 2007).

After an average period of 37 months after the end of type ALL-BFM 90 chemotherapy protocol, out of 52 patients almost half were overweight, nearly 6% - obese, more than half had at least one risk factor for MS, and about 6% had MS (Kourti et al., 2005).

It was found that the consequences of treatment performed for ALL during childhood may become manifest when subjects reach adulthood. Cranial irradiation favors more the appearance of MS: 60% of those who had been so treated had at least two of the five components of MS when they become adults, and only 20% of those who had not been irradiated. The pathogenetic mechanism that explains the metabolic effects of cranial irradiation implies growth hormone (GH) deficiency, lower level of insulin-like growth factor 1, fasting hyperinsulinemia, abdominal obesity and hyperlipidemia, especially in women (Gurney et al., 2006). In another study, ALL survivors who received cranial irradiation developed more frequently MS than those nonirradiated (23% towards 7%), probably because of higher prevalence of excess weight and arterial hypertension (van Waas et al., 2010).

Cholesterol and Triglycerides Metabolism Disorder in Malignant Hemopathies 395

In the regulation of lipid and CH metabolism liver X receptors are also involved, they are nuclear receptors. They can modulate the proliferation and survival of both normal and

The correlation between increasing CH in lipid domains and the possible cancerosus cell transformation is very interesting (Ajith et al., 2008). It is believed that CH is important for cell proliferation, because low serum CH values may be the result of high cellular CH need of cancerous cells. Low serum CH values correlate with elevated levels of CH in lymphocytes. Evidence of low levels of CH in the culture medium is due to the development of lymphoma cells, which would consume more CH for their own proliferation. The experimental administration of mevastatin in vitro, which inhibits CH synthesis, did not determine a significant variation of the concentration of CH in the culture medium, while

Low serum CH levels are also frequently found in acute leukemia patients. These patients have significantly lower serum values of CH, HDL-cholesterol, and LDL-cholesterol. A possible explanation for the low levels of HDL-cholesterol in the patients with acute leukemia could be an increased expression of a possible selective site for HDL-cholesteryl

Malignant, proliferative cells have an intense metabolism of CH, while decreased intake of CH is responsible for decreasing cell proliferation. In a human line of promyelocytic HL-60 cells, an inhibition of cell cycle progression from G2 phase can be obtained by an enzymatic inhibition of CH synthesis at a stage before 7-dehydrocholesterol production. Drugs such as zaragozic acid or SKF 104976 can induce the expression of antigen 11c, a cluster of differentiation. These products have a comparable action to all-trans retinoic acid, which

Chronic lymphocytic leukemia (CLL) is a heterogenous malignant hemopathy. In these patients, in the presence of UM-IGHV, which is a negative prognostic factor, there are increased levels of CH and lactate and low levels of glycerol and 3-hydroxybutyrate.

CD5 antigen is responsible for CH synthesis and even for adipogenesis. It is known that malignant cells from CLL are undergoing a process of continuous stimulation due to CD5 activation and cell survival. (Gary-Gouy et al., 2007) A continuous activation of an antiapoptotic pathway explains the CLL cells survival. Apolipoprotein E4-very low density lipoproteins is responsible for the high level of apoptosis in CLL cells. Lipoprotein lipase is the enzyme that metabolizes very low density lipoproteins to low-density lipoprotein. It was observed that an increase of lipoprotein lipase mRNA levels is present in CLL patients with

CH synthesis is also increased in patients with T-ALL who are glucocorticoid resistant

The growth of a promyelocytic leukemia cell line – HL-60 can be experimentally supressed by sodium cholesteryl sulfate, cholesteryl bromide, and cholesteryl-5alpha. The first two are responsible for the cell arrest in S and G2/M phases, and the last product – in the G2/M

It was found that in xenotransplanted severely combined immunodeficient mice the most abundant bone marrow CH amounts are located in leukemia-rich sites. In vitro, in leukemic cells CH is able to stimulate FLT-1 expression and VEGF production. Human leukemic cells from patients with AML are significantly richer in CH than normal cells and this CH

augmentation represents a marker of aggressive evolution. (Casalou et al., 2011)

malignant B and T lymphocytes. (Geyeregger et al., 2009)

induces monocyte differentiation. (Sánchez-Martín et al., 2007)

cell growth diminished. (Pugliese et al., 2010)

ester. (Gonçalves et al., 2005)

(MacIntyre et al., 2010)

(Beesley et al., 2009).

phase. (Ishimaru et al., 2008)

shorter survival. (Weinberg et al., 2008)

In a study conducted on a group of 184 adults who had ALL in their childhood, the overall prevalence of MS has been even higher - 9.2%. Peripheral stem cell allografts after total body irradiation favored the occurrence of hypertriglyceridemia, low HDL-cholesterol and increased fasting glucose level (Oudin et al., 2011).

In Sweden a group of adults was analysed; they survived after ALL during childhood and were submitted to radio-and chemotherapy. Those who received treatment for 5 years with GH compared with those not treated so for 8 years, showed significant changes in HDLcholesterol, glucose and apolipoprotein B / apolipoprotein A1 ratio, and MS was significantly less frequent. (Follin et al., 2010)

Another study conducted in Sweden on adults who had childhood leukemia, found an augmentation of total body fat, especially of trunk adiposity and an evolution towards an unfavorable lipid spectrum. These observations were correlated with low levels of endocrine secretion of GH, a consequence of previous cranial irradiation. (Jarfelt et al., 2005) An interesting combination of diseases was described in a 54 years old woman: after being diagnosed with chronic neutrophilic leukemia a liver biopsy was made. The histopathological diagnosis was of nonalcoholic steatohepatitis (NASH) with neutrophilic

infiltrate. The authors consider that the leukemia cells that infiltrated the liver contributed to the emergence of NASH. The administration of cytosine arabinoside contributed to a significant decrease in fat degeneration. (Yoshida et al., 2004)

There are few studies on the metabolism of chylomicrons in patients with cancer. The study of a group of patients with Hodgkin and nonHodgkin lymphoma, as compared to a healthy control group, led to the observation that after an intravenous administration of a chylomicron-like emulsion, the levels of CH, TG and VLDL were significantly higher in patients with lymphoma because of the profound disturbance of the chylomicrons lipolysis and their removal deficit. (Gonçalves et al., 2003)

A very interesting observation was achieved in a line of promyelocytic leukemia NB4 cells: the administration of peroxisome proliferator-activated receptor gamma ligands was able not only to induce differentiation but also to favor lipogenesis in NB4 cells. This fact suggests a close link between differentiation and lipogenesis process in human myeloid cells thus stimulated. (Yasugi et al., 2006).
