Table 1 Classfication and clinical features of MPL mutations indentified in hematopoietic diseases
From: Different mutations of the human c-mpl gene indicate distinct haematopoietic diseases
Mutation type | Mutation and Inheritance pattern | Effect | clinical manifestation | Disease (mutation rate) | Reference |
|---|---|---|---|---|---|
Type 1 41 different MPL mutations in CAMT | Autosomal recessive Germline mutation | Completely lose or significantly reduce MPL function | Thrombocytopenia | CAMT (about 91.8%) | (25-30) |
Type 2 S505N | Autosomal dominant Germline mutation, rare somatic mutation | Autonomous activate MPL function | Thrombocytosis | HT (about 54.5%) | (22,24,34,35) |
K39N,P106L | Autosomal dominant with incomplete penetrance and autosomal recessive with possible mild heterozygote manifestation germline mutation | Reduce binding affinity to ligand thrombopoietin | Thrombocytosis | HT (7% of African-American individuals and 6% of Arab individuals) | (40,41) |
Type 3 W515L/K | Somatic mutation | Autonomous activate MPL function | Thrombocytosis | MPNs (about1% in ET and 5% in PMF, rare in PV), AMKL with myelofibrosis (about 25%),rare in RARS-t | (48-50,57,59,66-69) |
Type 4 W515A/R, T487A,Y252H | Somatic mutation | Autonomous activate MPL function | Thrombocytosis | Rare in MPNs、 AMKL and ET respectively | (52,57,59,70,71) |
A519T,L510P and A506T | Somatic mutation | No function or maybe regulate other genetic events. | Unknown | Rare in PMF | (57) |
W515-P518delinsKT, Y591D,S204P/F, IVS 11/12 and IVS 10/11 | Somatic mutation | Unclear | Unknown | Rare in MPNs | (72-74) |