hematology
Contributions
Type: Publication Only
Background
CALR mutation discovery improves essential thrombocythemia (TE) and idiopathic myelofibrosis (MI) diagnosis. Over 36 CALR type mutations have been found, but only two types (type 1: del52bp and type 2: ins5bp) are present in 80% of the patients. It seems that type 1 mutation is frequently associated to fibrosis and that it has a worse impact on overall survival than type 2 mutation. Diagnosis of a prefibrotic state (MF0) presents histological diagnostic difficulties. MF0 has a worse prognostic impact than TE with regard to thrombotic risk, and a higher risk towards MI and acute leukemia evolution. For this reason a new type of identification of a group of patients is very useful.
Aims
The aim of this study was to evaluate CALR mutations in patients with MI and TE JAK2-negative and MPL-negative and the type of CALR mutations frequently associated to MF0.
Methods
We studied 47 patients CALR-positive, 21 with TE and 26 with MI. 12 out of 26 with MI were classified as MF0 on the basis of the histological examination of bone marrow biopsy. Debut features have been evaluated for WBC, Hb, PLT, LDH, peripheral CD34, spleen. Fragment analysis of PCR exone 9 CALR gene was performed.
Results
Type 1 mutation was present in 6 out of 21 patients (30%) with TE and in 19 out of 26 patients (73%) with MI. In the subgroup of MF0, 9 patients out of 12 (75%) were positive to del52bp. Conversely, type 2 mutation was present in 15 patients out of 21 (70%) with TE and in only 7 patients out of 26 (27%) with MI. Of the 12 patients with MF0, 3 patients (25%) were positive to ins5bp. Statistical analysis was negative for WBC, Hb, PLT, LDH, peripheral CD34 and spleen and not statistically significant between these 3 groups of patients.
Summary
It was recognized that CALR mutation has a better impact with respect to the complications of myeloproliferative neoplasm Ph1 negative. It is still unclear the role of del and ins mutations of CALR gene. In our experience, type 1 mutation is more representative in “fibrotic” phenotype as it is demonstrated the higher frequence of del 52bp in MF0 patients than in MI patients. This allowed us to better identify MF0 clinical features, in that a particular clinical attention for MF0 is required, being different from TE.
Keywords: MF0, CALR, CALR mutations, TE
Session topic: Publication Only
Type: Publication Only
Background
CALR mutation discovery improves essential thrombocythemia (TE) and idiopathic myelofibrosis (MI) diagnosis. Over 36 CALR type mutations have been found, but only two types (type 1: del52bp and type 2: ins5bp) are present in 80% of the patients. It seems that type 1 mutation is frequently associated to fibrosis and that it has a worse impact on overall survival than type 2 mutation. Diagnosis of a prefibrotic state (MF0) presents histological diagnostic difficulties. MF0 has a worse prognostic impact than TE with regard to thrombotic risk, and a higher risk towards MI and acute leukemia evolution. For this reason a new type of identification of a group of patients is very useful.
Aims
The aim of this study was to evaluate CALR mutations in patients with MI and TE JAK2-negative and MPL-negative and the type of CALR mutations frequently associated to MF0.
Methods
We studied 47 patients CALR-positive, 21 with TE and 26 with MI. 12 out of 26 with MI were classified as MF0 on the basis of the histological examination of bone marrow biopsy. Debut features have been evaluated for WBC, Hb, PLT, LDH, peripheral CD34, spleen. Fragment analysis of PCR exone 9 CALR gene was performed.
Results
Type 1 mutation was present in 6 out of 21 patients (30%) with TE and in 19 out of 26 patients (73%) with MI. In the subgroup of MF0, 9 patients out of 12 (75%) were positive to del52bp. Conversely, type 2 mutation was present in 15 patients out of 21 (70%) with TE and in only 7 patients out of 26 (27%) with MI. Of the 12 patients with MF0, 3 patients (25%) were positive to ins5bp. Statistical analysis was negative for WBC, Hb, PLT, LDH, peripheral CD34 and spleen and not statistically significant between these 3 groups of patients.
Summary
It was recognized that CALR mutation has a better impact with respect to the complications of myeloproliferative neoplasm Ph1 negative. It is still unclear the role of del and ins mutations of CALR gene. In our experience, type 1 mutation is more representative in “fibrotic” phenotype as it is demonstrated the higher frequence of del 52bp in MF0 patients than in MI patients. This allowed us to better identify MF0 clinical features, in that a particular clinical attention for MF0 is required, being different from TE.
Keywords: MF0, CALR, CALR mutations, TE
Session topic: Publication Only