Contributions
Abstract: PB2303
Type: Publication Only
Background
Recently, somatic mutations in CALR gene have been demonstrated to be the second most common driver mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF). Approximately 50 different indels have been found in exon 9 of the CALR gene but more than 80% of CALR mutated patients possess one of the two most frequent variants: a 52-bp deletion (p.Leu367fs*46; type 1) and a 5-bp insertion (p.Lys385fs*47; type 2 mutation). An 80-year-old male patient with thrombocythemia was investigated for CALR mutation to confirm his clinical diagnosis of primary myelofibrosis. The patient carried both of the two most frequent types of CALR mutations (type 1 and type 2).
Aims
Verification of rare findings in CALR gene by MLPA assay and their interpretation considering the recent studies and clinical data of the patient.
Methods
In our laboratory the routine detection of the CALR mutations is performed by a fragment analysis on capillary electrophoresis. Positive results are confirmed by Sanger sequencing. However, sequencing data were not clear in this case (presence of deletion and insertion in one amplicon). Therefore we chose SALSA MLPA probemix P520-A2 MPN mix 2 for successfull verification of our findings (Figure 1).
Results
Presence of CALR mutation was one of the three major WHO diagnostic criteria of prePMF for this patient. Mostly, ET and PMF patients carry only one CALR mutation. Suprisingly, we found a patient with two variants: type 1 and type 2 mutation. MLPA and Sanger sequencing were used to verify our findings gained from fragment analysis, but only MLPA assay clearly confirmed the presence of two mutations. In our patient anamnesis the several diseases of urinary system were mentioned (subglandular hypospadia, kidney cysts, carcinoma of kidney) and the patient underwent radiotherapy due to carcinoma of prostate gland in 2010. The PMF diagnosis was established in 2017 with subsequent moderate progress.
Conclusion
The moderate progress of PMF is associated with prognostic benefit, which is described in patients with CALR mutation, particularly with type 1 cases. Both types of CALR mutaions in one patient have been already mentioned but without any clarification of its development or impact on the PMF prognosis. In the case of our patient, it seems to be moderate progress of PMF yet. As generally known, radioactivity increased a risk of myeloproliferative neoplasms. Therefore we suppose that the radiotherapy could influenced the development of PMF with the sporadic presence of two CALR mutations.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Abstract: PB2303
Type: Publication Only
Background
Recently, somatic mutations in CALR gene have been demonstrated to be the second most common driver mutations in essential thrombocythemia (ET) and primary myelofibrosis (PMF). Approximately 50 different indels have been found in exon 9 of the CALR gene but more than 80% of CALR mutated patients possess one of the two most frequent variants: a 52-bp deletion (p.Leu367fs*46; type 1) and a 5-bp insertion (p.Lys385fs*47; type 2 mutation). An 80-year-old male patient with thrombocythemia was investigated for CALR mutation to confirm his clinical diagnosis of primary myelofibrosis. The patient carried both of the two most frequent types of CALR mutations (type 1 and type 2).
Aims
Verification of rare findings in CALR gene by MLPA assay and their interpretation considering the recent studies and clinical data of the patient.
Methods
In our laboratory the routine detection of the CALR mutations is performed by a fragment analysis on capillary electrophoresis. Positive results are confirmed by Sanger sequencing. However, sequencing data were not clear in this case (presence of deletion and insertion in one amplicon). Therefore we chose SALSA MLPA probemix P520-A2 MPN mix 2 for successfull verification of our findings (Figure 1).
Results
Presence of CALR mutation was one of the three major WHO diagnostic criteria of prePMF for this patient. Mostly, ET and PMF patients carry only one CALR mutation. Suprisingly, we found a patient with two variants: type 1 and type 2 mutation. MLPA and Sanger sequencing were used to verify our findings gained from fragment analysis, but only MLPA assay clearly confirmed the presence of two mutations. In our patient anamnesis the several diseases of urinary system were mentioned (subglandular hypospadia, kidney cysts, carcinoma of kidney) and the patient underwent radiotherapy due to carcinoma of prostate gland in 2010. The PMF diagnosis was established in 2017 with subsequent moderate progress.
Conclusion
The moderate progress of PMF is associated with prognostic benefit, which is described in patients with CALR mutation, particularly with type 1 cases. Both types of CALR mutaions in one patient have been already mentioned but without any clarification of its development or impact on the PMF prognosis. In the case of our patient, it seems to be moderate progress of PMF yet. As generally known, radioactivity increased a risk of myeloproliferative neoplasms. Therefore we suppose that the radiotherapy could influenced the development of PMF with the sporadic presence of two CALR mutations.
Session topic: 16. Myeloproliferative neoplasms - Clinical