Abstract

Among 281 patients with essential thrombocythemia and calreticulin (CALR) mutation, we found a variant allele frequency of ≥60% to be associated with significantly shortened myelofibrosis-free survival, mostly apparent with CALR type-1 and CALR type-indeterminate mutations.

1.
Nangalia
J
,
Massie
CE
,
Baxter
EJ
, et al
.
Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2
.
N Engl J Med
.
2013
;
369
(
25
):
2391
-
2405
.
2.
Klampfl
T
,
Gisslinger
H
,
Harutyunyan
AS
, et al
.
Somatic mutations of calreticulin in myeloproliferative neoplasms
.
N Engl J Med
.
2013
;
369
(
25
):
2379
-
2390
.
3.
Guglielmelli
P
,
Maccari
C
,
Sordi
B
, et al
.
Phenotypic correlations of CALR mutation variant allele frequency in patients with myelofibrosis
.
Blood Cancer J
.
2023
;
13
(
1
):
21
.
4.
Stengel
A
,
Jeromin
S
,
Haferlach
T
,
Meggendorfer
M
,
Kern
W
,
Haferlach
C
.
Detection and characterization of homozygosity of mutated CALR by copy neutral loss of heterozygosity in myeloproliferative neoplasms among cases with high CALR mutation loads or with progressive disease
.
Haematologica
.
2019
;
104
(
5
):
e187
-
e190
.
5.
Khoury
JD
,
Solary
E
,
Abla
O
, et al
.
The 5th edition of the World Health Organization classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms
.
Leukemia
.
2022
;
36
(
7
):
1703
-
1719
.
6.
Arber
DA
,
Orazi
A
,
Hasserjian
RP
, et al
.
International Consensus Classification of myeloid neoplasms and acute leukemias: integrating morphologic, clinical, and genomic data
.
Blood
.
2022
;
140
(
11
):
1200
-
1228
.
7.
Thiele
J
,
Kvasnicka
HM
,
Orazi
A
, et al
.
The International Consensus Classification of myeloid neoplasms and acute leukemias: myeloproliferative neoplasms
.
Am J Hematol
.
2023
;
98
(
3
):
544
-
545
.
8.
Barosi
G
,
Mesa
RA
,
Thiele
J
, et al
.
Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for myelofibrosis research and treatment
.
Leukemia
.
2008
;
22
(
2
):
437
-
438
.
9.
Guglielmelli
P
,
Lasho
TL
,
Rotunno
G
, et al
.
MIPSS70: mutation-enhanced international prognostic score system for transplantation-age patients with primary myelofibrosis
.
J Clin Oncol
.
2018
;
36
(
4
):
310
-
318
.
10.
Tefferi
A
,
Wassie
EA
,
Guglielmelli
P
, et al
.
Type 1 vs type 2 calreticulin mutations in essential thrombocythemia: a collaborative study of 1027 patients
.
Am J Hematol
.
2014
;
89
(
8
):
e121
-
124
.
11.
Rumi
E
,
Pietra
D
,
Ferretti
V
, et al
.
JAK2 or CALR mutation status defines subtypes of essential thrombocythemia with substantially different clinical course and outcomes
.
Blood
.
2014
;
123
(
10
):
1544
-
1551
.
12.
Rotunno
G
,
Mannarelli
C
,
Guglielmelli
P
, et al
.
Impact of calreticulin mutations on clinical and hematological phenotype and outcome in essential thrombocythemia
.
Blood
.
2014
;
123
(
10
):
1552
-
1555
.
13.
Barbui
T
,
Vannucchi
AM
,
Buxhofer-Ausch
V
, et al
.
Practice-relevant revision of IPSET-thrombosis based on 1019 patients with WHO-defined essential thrombocythemia
.
Blood Cancer J
.
2015
;
5
(
11
):
e369
.
14.
Passamonti
F
,
Thiele
J
,
Girodon
F
, et al
.
A prognostic model to predict survival in 867 WHO-defined essential thrombocythemia at diagnosis: a study by the IWG-MRT
.
Blood
.
2012
;
120
(
6
):
1197
-
1201
.
15.
Loscocco
GG
,
Guglielmelli
P
,
Gangat
N
, et al
.
Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: a multicenter study involving 1607 patients
.
Am J Hematol
.
2021
;
96
(
11
):
1472
-
1480
.
16.
Vannucchi
AM
,
Antonioli
E
,
Guglielmelli
P
, et al
.
Clinical profile of homozygous JAK2V617F mutation in patients with polycythemia vera or essential thrombocythemia
.
Blood
.
2007
;
110
(
3
):
840
-
846
.
17.
Passamonti
F
,
Rumi
E
,
Pietra
D
, et al
.
A prospective study of 338 patients with polycythemia vera: the impact of JAK2 (V617F) allele burden and leukocytosis on fibrotic or leukemic disease transformation and vascular complications
.
Leukemia
.
2010
;
24
(
9
):
1574
-
1579
.
18.
Bertozzi
I
,
Biagetti
G
,
Vezzaro
T
, et al
.
Clinical effect of CALR allele burden in patients with essential thrombocythemia
.
Ann Hematol
.
2022
;
101
(
6
):
1345
-
1346
.
19.
Barbui
T
,
Thiele
J
,
Passamonti
F
, et al
.
Initial bone marrow reticulin fibrosis in polycythemia vera exerts an impact on clinical outcome
.
Blood
.
2012
;
119
(
10
):
2239
-
2241
.
20.
Reis
E
,
Buonpane
R
,
Celik
H
, et al
.
Discovery of INCA033989, a monoclonal antibody that selectively antagonizes mutant calreticulin oncogenic function in myeloproliferative neoplasms (MPNs)
.
Blood
.
2022
;
140
(
suppl 1
):
14
-
15
.
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