Abstract Number: PB0346
Meeting: ISTH 2021 Congress
Background: Most of the defined mutations in exon 9 of CALR gene are indels, with the exception of a few non-recurrent point mutations. More than 50 different CALR indels have been described including 52-bp deletion (p.L367fs*46) as type 1 and 5-bp TTGTC insertion (p.K385fs*47) as type 2 which are more frequent mutations. These different types of mutations in CALR exon 9 are thought to present different phenotypes.
Aims: To investigate the frequency of different types of calreticulin mutations in classical MPNs and to study statistical difference in their presentation.
Methods: Bi-directional Sanger sequencing detected CALR exon 9 mutations in total 28 MPNs patients (ET=19, PMF=9).
Results: 
| ET | PMF | ||||||||
| CALR +ve (N = 19) (A) |
Type 1 (N = 9) (B) |
Type 2 (N = 8) C |
CALR +ve (N = 9) (D) |
Type 1 (N = 6) (E) |
Type 2 (N = 2) (F) |
P-value | |||
| B vs C | E vs F | A vs D | |||||||
| Gender, No. (%) | |||||||||
| Male | 14(73.7) | 7(77.8) | 6(75) | 8(88.9) | 5(83.3) | 2(100) | 0.893 | 0.537 | 0.360 |
| Female | 5(26.3) | 2(22.2) | 2(25) | 1(11.1) | 1(16.6) | 0(0) | |||
| Age(in years) Mean (± SD) |
41.8(±12.9) | 40.4(±14.7) | 39.2(±9.5) | 51.8(±14.1) | 55.3(±15) | 38.5(±2.1) | 0.848 | 0.184 | 0.074 |
| Haemoglobin (g/dl) Mean (± SD) |
11.7(±2.4) | 11.5(±2.6) | 12.3(±2.0) | 11.0(1.3) | 11.2(±1.5) | 11.0(±1.4) | 0.509 | 0.876 | 0.457 |
| Leukocyte count ( x 109/L) Mean (± SD) |
9.9(±4.2) | 9.98(±5.57) | 9.4(±3.10) | 11.6(±7.09) | 14.0(±7.7) | 7.07(±2.0) | 0.805 | 0.280 | 0.433 |
| Platelet count ( x 109/L) Mean (± SD) |
1254 (±602) | 1116(±601) | 1317(±562) | 472(±432) | 502(±501) | 535(±370) | 0.490 | 0.936 | 0.002 |
Among various CALR mutation types, type 1 was observed more common (53.5%; 15/28) in ET and PMF collectively compared to type 2 (35.7%; 10/28). In ET type-1 CALR mutation was found in 47.3% (9/19) of patients and two of them had two novel scattered point mutations (c.1081C>G p.Gln361Glu and c.1086C>G p.Asp362Glu) at upstream and type-2 was in 42.1 % (8/19) of patients. Mutations in ET other than type 1 and 2 were 10.5% (2/19) comprising a novel double deletion of 10bp (c.1130_1139del p.Lys377ArgfsTer50) and 28bp (1195_1222del p.Glu399MetfsTer2) in a patient and one known CALR 12bp deletion (c.1214_1225del; p.Glu405_Asp408del) in another patient. In PMF type-1 CALR mutation was found in 66.6% (6/9) patients and type-2 in 22.2% (2/9) of patients whereas one patient harbored novel homozygous CALR mutation (c.1139delA p.Glu380lyfsTer50).
There was no significant difference observed in terms of gender, mean age and haematological parameters of CALR positive type 1 and type 2 in ET and PMF.
Conclusions: This study reported a complex mutation, a novel double deletion of CALR and at upstream of type 1 CALR two novel single nucleotide variants.
To cite this abstract in AMA style:
Ahmed R, Rashid M, Zaidi U, Shmasi T. Frequency and Clinical Significance of Different Types of Calreticulin (CALR) Mutations in Myeloproliferative Neoplasms (MPNs): A Cohort of Patients from Pakistan [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/frequency-and-clinical-significance-of-different-types-of-calreticulin-calr-mutations-in-myeloproliferative-neoplasms-mpns-a-cohort-of-patients-from-pakistan/. Accessed October 1, 2023.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/frequency-and-clinical-significance-of-different-types-of-calreticulin-calr-mutations-in-myeloproliferative-neoplasms-mpns-a-cohort-of-patients-from-pakistan/