title: Gene expression profiling identifies ARSD as a new marker of disease progression and the sphingolipid metabolism as a potential novel metabolism in chronic lymphocytic leukemia.
abstract: BACKGROUND
  Several studies demonstrated IGVH mutational status and ZAP70 expression as the most relevant prognostic markers in Chronic Lymphocytic Leukemia (CLL), suggesting the separation of two patient subgroups: with good mutated ZAP70 negative (MTZAP70(-) and poor unmutated ZAP70 positive (UMZAP70(+)) prognosis.
  
  
  METHODS
  We determined the gene expression of B cells in 112 CLL patients divided into three classes: class 1 with MTZAP70(-), class 2 with UMZAP70(+), and class 3 included both UMZAP70(-) and MTZAP70(+).
  
  
  RESULTS
  We found LPL, AGPAT2, MBOAT1, CHPT1, AGPAT4, PLD1 genes encoding enzymes involved in lipid metabolism overexpressed in UMZAP70(+). In addition, this study identified ARSD, a gene belonging to the sphingolipid metabolism, as a new gene significantly overexpressed in UMZAP70(+) compared to MTZAP70(-). Western blots confirmed that ARSD protein levels were significantly different between the 3 classes of patients and normal controls. Statistical analysis identified a significant correlation between ARSD and IGVH; however, both ARSD protein level and IGVH were independently associated with the need for therapy of CLL patients.
  
  
  CONCLUSIONS
  ARSD is a novel prognostic factor as the time to start therapy is shorter in patients with high levels of ARSD protein and sphingolipid metabolism could represent a new biological mechanism in CLL.
authors: Department of Oncology, Division of Hematology, Niguarda Hospital, Milan, Italy. alessandra.trojani@ospedaleniguarda.it
authors: Alessandra
authors: A
authors: Trojani
authors: Barbara
authors: B
authors: Di Camillo
authors: Alessandra
authors: A
authors: Tedeschi
authors: Milena
authors: M
authors: Lodola
authors: Simona
authors: S
authors: Montesano
authors: Francesca
authors: F
authors: Ricci
authors: Eleonora
authors: E
authors: Vismara
authors: Antonino
authors: A
authors: Greco
authors: Silvio
authors: S
authors: Veronese
authors: Aldo
authors: A
authors: Orlacchio
authors: Sabata
authors: S
authors: Martino
authors: Chiara
authors: C
authors: Colombo
authors: Mariangela
authors: M
authors: Mura
authors: Michele
authors: M
authors: Nichelatti
authors: Anna
authors: A
authors: Colosimo
authors: Barbara
authors: B
authors: Scarpati
authors: Marco
authors: M
authors: Montillo
authors: Enrica
authors: E
authors: Morra
mesh_terms: D000328:Adult; D000368:Aged; D001192:Arylsulfatases / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D005796:Genes; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D053208:Kaplan-Meier Estimate; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D013107:Sphingolipids / Q000378:metabolism*; D059467:Transcriptome; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D007143:Immunoglobulin Heavy Chains; D013107:Sphingolipids; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C576379:ARSD protein, human; D001192:Arylsulfatases