Konference: 2015 20th Congress of the European Hematology Association - účast ČR

Kategorie: Maligní lymfomy a leukémie

Téma: Publication only

Číslo abstraktu: PB1841

Autoři: Maria Pamela Dalamaga; Antigoni Lekka; Maria Triantafilli; G. C. Sotiropoulos; John Chamberland; Konstantinos Karmaniolas; Lambros Tzianoumis; Christos Mantzoros

Recent evidence suggests that overweight/obesity may be implicated in the etiology of hematologic malignancies, including myelogenous leukemia and myelodysplastic syndromes. A strong asociation of overweight/obesity with insulin resistance, characterized by hyperinsulinemia, has been well documented. There is evidence that insulin resistance is implicated in several malignancies associated with excess body weight. Leptin and, particularly, free leptin, the biologically significant form of leptin, reflecting accurately the body fat mass, regulate glucose and lipid metabolism by ameliorating insulin sensitivity and decreasing intracellular lipids. 

In this cross-sectional study, we investigated the potential association of leptin and free leptin with chronic myelomonocytic leukemia (CMML), a hematologic malignancy combining proliferative and dysplastic features, after adjusting for a potential confounding effect of age,gender, date of diagnosis (matching factors) a well as withbody mass index (BMI), family history of lymphohematopoietic cancer (LHC) and serum insulin.


Blood samples were collected from 14 cases with incident, histologically confirmed CMML and 70 healthy controls (in an analogy of one patient versus five healthy controls) who came for an annual check-up examination without any neoplastic and infectious conditions, matched on gender, age and year/month of diagnosis (±1 month) between 2004-2012. Informed consent was obtained from all study participants. Serum leptin and insulin were determined by radioimmunoassay (Linco Research Institute St Louis MO, and Millipore Co Billerica, MA respectively). Serum leptin receptor levels (sOB-R) levels were measured using a commercially available ELISA (BioVendor R&D, Brno, Czech Republic). Free Leptin Index (FLI) was calculated as the ratio of leptin to sOBR. The statistical analysis of the data was performed using IBM-SPSS® version 22 for Windows.


CMML cases presented significantly higher height and weight than control subjects (p<0.001), while differences of BMI were only of borderline significance (p=0.10). Serum insulin was significantly higher in cases than controls (p=0.05). CMML cases exhibited a significant total and free hypoleptinemia in comparison to controls (total leptin in patients with CMML: 13.2 ± 16.3 ng/mL versus controls 24 ± 21.1 ng/mL, p=0.005; FLI in patients with CMML: 0.81 ± 1.6 versus controls: 2.84 ± 5.4, p=0.04). Moreover, CMML cases exhibited significantly lower serum levels of sOB-R than controls (p=0.04). In multivariate analysis, subjects with total and free hypoleptinemia presented significantly higher odds for CMML after adjusting for age, gender, date of diagnosis, BMI, family history of LHC and serum insulin levels.  

This study raises the hypothesis that leptin which reflects overall fat mass and insulin may be associated with CMML. Leptin’s major physiological role is to signal inadequate rather than excess energy stores, and hypoleptinemia found in a small but significant percentage of obese humans is associated with hyperinsulinemia and impaired T-cell function. Further mechanistic, interventional and epidemiological studies are needed to confirm these findings and to explore whether leptin may mediate the effect of body fat distribution on insulin resistance and leukemogenesis risk.

Keyword(s): Chronic myelomonocytic leukemia, Myeloproliferative disorder, Obesity

Datum přednesení příspěvku: 12. 6. 2015