Serum Tryptase Levels in AML at Diagnosis: A Multicenter Retrospective Study.

Abstract

α and β-tryptase genes cluster on the short arm of human chromosome 16 and encode lineage-associated serine proteases that are abundantly expressed in mast-cells and, in trace amounts, in basophils. Under physiologic conditions no other myeloid cells express tryptases. However, in several myeloid leukemia cell lines and in AML blasts, the level of tryptase is elevated. In an attempt at correlating the levels of tryptase with cytogenetic features and the KIT and FLT3 mutational status, we analyzed serum samples collected at diagnosis from 150 AML and 57 ALL adult patients. The total serum concentration was determined by UniCAP 100 and UniCAP Tryptase Fluorenzyme Immunoassay Kit (Pharmacia-Upjohn, Uppsala, Sweden). The median value of tryptase level in the control group (50 healthy people; mean age 35 y, range 20–50; M/F= 26/24) amounted to less than 5 ng/ml, ranging from 1 to 15 ng/ml. We detected elevated tryptase levels (more than 15 ng/ml) in 66 out of 150 AML-patients (44%) and in 1 out of 57 ALL-patients (1.75%; median value 1.2 ng/ml) (p = < 0.0005, Fisher's exact test ). In AMLs data showed that elevated tryptase values are significantly bound to patients with t(8;21) (n = 26, p = <0.0001) and inv(16) (n = 17, p = 0.035). Furthermore, we found a strong correlation between tryptase < 15 ng/ml and normal karyotype (n = 58 ; p = <0.0001). By contrast, we didn't find any correlation between the levels of tryptase and t(15;17) (n = 12, p = 0.227), abnormal chr 5 or 7 (n = 9, p = 0.507), +8 (n = 6, p = 0.229), complex karyotype (n = 9, p = 1.000) or other abnormalities (n = 14, p = 0.778). A mutational screening for KIT (exon 2,8,10,11,and 17) and FLT3 (exon 14,15 and 20) was performed on 67/150 (45%) and 82/150 (55%) patients with AML, respectively. We recorded a significant association between high tryptase levels and the presence of KIT mutation (Fisher's exact test: p = 0.012). No correlation was found between levels of tryptase and FLT3 mutational status (Fisher's exact test: p = 0.803).In conclusion, data suggest that elevated serum tryptase levels at diagnosis are frequently associated with Core Binding Factor and with KIT mutated AML's.