Primary myelofibrosis with concurrent CALR and MPL mutations: A case report

Abstract

Background: Primary myelofibrosis (PMF) is a myeloproliferative neoplasm (MPN) characterized by recurrent mutations in the JAK2, CALR, and MPL genes. The CALR and MPL co-mutation is very rare. To our knowledge, no more than five cases have been reported. Here, we report a case of PMF in which a CALR and MPL co-mutation was detected by next-generation sequencing (NGS) technology, and a literature review was performed.

Case summary: A 73-year-old woman was admitted to our hospital in 2018 due to abdominal distension. The patient had splenomegaly, lymphadenopathy, leukopenia, anemia, and immature granulocytes in peripheral blood. There were dacrocytes and atypical megakaryocytes in bone marrow, and megakaryocytic proliferation was very active, accompanied by reticulin fibrosis grade 2. By NGS analysis of the bone marrow sample, we detected mutations in CALR, MPL, and PIK3RI, while JAK2 V617F and BCR-ABL were negative. Therefore, the patient was diagnosed with PMF and received oral ruxolitinib. However, the spleen and hematologic responses were poor. We review the literature, analyze previous reports of the mutation sites in our patient and differences between our patient and other reported cases of co-mutated CALR and MPL genes, and discuss the reason why the CALR and MPL co-mutations are rare and possible mechanisms and their impact on the prognosis of patients.

Conclusion: CALR and MPL mutations can be concurrent in MPN, but they are rare. The use of NGS may help to identify more patients with co-mutated CALR and MPL genes. This will help to further explore the mechanism and its impact on these patients to develop appropriate treatment strategies.

Keywords: CALR; Case report; Co-mutation; MPL; Next-generation sequencing; Primary myelofibrosis.

Figure 1

Computed tomography images showing splenomegaly. A and B: Abdominal computed tomography images showing that the inferior margin of the spleen was lower than that of the liver (A) and reached the level of abdominal aortic bifurcation (B).

Figure 2

Bone marrow aspiration findings. A: Dacrocytes were easily observed; B-D: Images showing the presence of megakaryocyte atypia, including abnormal nuclear-cytoplasmic ratios, malformed nucleus (B), abnormal chromatin clumping with hyperchromatic nucleus (C), and extensive lobulation of the nucleus (D).

Figure 3

Bone marrow biopsy findings. A: Hematoxylin and eosin staining showed megakaryocytic proliferation and clustered distribution (magnification, 200 ×); B: Gomori staining showed diffuse and dense increase in reticulin fibres (magnification, 200 ×).