Bonroy, Carolien

Daneels, Willem

De Maertelaere, Emilie

Delie, Anke

Denys, Barbara

Devreese, Katrien

Moors, Ine

Philippé, Jan

Van der Meulen, Joni

Van Dorpe, Jo

Van Roy, Nadine

Vandepoele, Karl

English

Ghent University Academic Bibliography

A CASE REPORT OF ACUTE PANMYELOSIS WITH MYELOFIBROSIS(APMF) WITH A DISTINCT MOLECULAR PATTERN E. De Maertelaere1, K. Vandepoele1, J. Van der Meulen2, I. Moors3, W. Daneels3, A. Delie3, J. Philippé1, C. Bonroy1, K. Devreese1, N. Van Roy4, J. Van Dorpe5, B. Denys1CONTACTEMILIE DE MAERTELAERE+32 (0)9 332 03 54emilie.demaertelaere@uzgent.be1Department of Laboratory Medicine, Ghent University Hospital, Ghent, Belgium2Molecular Diagnostics Ghent University Hospital (MDG), Ghent University Hospital, Ghent, Belgium3Department of Hematology, Ghent University Hospital, Ghent, Belgium4Center for Medical Genetics, Ghent University Hospital, Ghent, Belgium5Department of Pathology, Ghent University Hospital, Ghent, BelgiumCONCLUSIONAPMF is a rare AML entity with a challenging diagnosis. Genetic alterationsassociated with this disease are not well studied. The variants present inthis patient underly the biology of the disease and can be of added value toconfirm the diagnosis.CASEDISCUSSIONA 67-year-old man presented with persisting fatigue and unexplained weight loss. The peripheral blood examination showed anemia (hemoglobin 8,6g/dL; normal range 12,9-17,3 g/dL) with normal platelet and white blood cell counts, and a blastic population (35%; figure 1A).In contrast to the hypocellular bone marrow aspirate (figure 1B), the biopsy revealed a markedly hypercellular marrow, with proliferation of the threelineages (i.e. panmyelosis) and 50% blasts (figure 1C). The megakaryocytes showed dysplastic features and a reticulin staining revealed myelofibrosis(grade 2-3; figure 1D). The blastic population showed expression of CD34, CD117, HLA-DR, CD13 and CD33, in the absence of cyMPO, T/B/NK cell andmonocytic markers (figure 2). According to the WHO 2016 classification, the diagnosis of an acute panmyelosis with myelofibrosis (APMF) was made.Next-generation sequencing (NGS) showed mutations in three genes: RUNX1, SRSF2 and CALR. Also, WT1 and EVI1 overexpression were found.Cytogenetic analysis revealed an aberrant karyotype with the presence of der(6)t(1;6)(q21;p21).Due to co-morbidities, low intensity chemotherapy (cytarabine) was started but discontinued after one cycle because of complications. Further treatmentwas palliative.APMF is a rare type of acute myeloid leukemia (AML), althoughprevalence might be underestimated due to the challenging diagnosis.The differential diagnosis includes acute megakaryoblastic leukemia,other AML with dysplastic changes, myelodysplastic syndrome withexcess blasts and primary myelofibrosis (PMF). Very little is knownabout the genetic profile of APMF.We performed NGS analysis on the bone marrow sample of genes thatare relevant in AML and in myeloproliferative disorders, considering themyelofibrosis. Following genes were included: ASXL1, CEBPA,DNMT3A, FLT3, IDH1, IDH2, KIT, NPM1, NRAS, RUNX1, SF3B1,SRSF2, TET2, TP53, U2AF1, JAK2, CALR and MPL. We detectedthree variants with this targeted NGS analysis, presented in table 1.The combination of a RUNX1 and SRSF2 variant is known to correlatewith a poor prognosis in AML (Gaidzik et al., Leukemia 2016).Frameshift mutations in CALR occur in myeloproliferative disorders andespecially type I is associated with myelofibrosis. Additionally,der(6)t(1;6)(q21;p21) has already been described in PMF (Hussein etal., European Journal of Haematology 2009). These findings arecompatible with the APMF diagnosis.Table 1. Overview of the detected variants in the bone marrow sample of the patient with APMFGene Variant type DNA Protein VAF(variant allelefrequency)RUNX1 Missense variant c.307C>G p.(Pro103Ala) 42.7%SRSF2 Missense variant in hotspot (P95H)c.284C>A p.(Pro95His) 34.7%CALR Frameshift variantin hotspot (type I)c.1099_1150del p.(Leu367Thrfs*46) 24.5%Figure 1. A. Blast in peripheral blood smear (x40). B. Hypocellular bone marrow aspirate (x10). C. Hypercellular bone marrow biopsy showing a focus of blasts and dysplasticmegakaryocytes of small size with atypical hyposegmented nuclei (hematoxylin andeosin, x40). D. Reticulin staining showing an obvious increase of coarse reticulin fibres (x20).A BC DCD45 PacO-ACD33 APC-ACD117 PE Cy7-AcyMPO FITC-AHLA-DR PacB-ACD7 APC-ASSC-ACD34 PerCPCy5-5-AFigure 2. Immunophenotyping of the bone marrow aspirate. Black: blasts; blue: granulocytes; orange: lymphocytes. The monocytes were absent, concordant with the cytomorphology.A. SSC versus CD45. The green population is debris.B. CD34 versus CD117. The majority of the granulocytes express CD117, i.e. immature granulocytes. C. HLA-DR versus CD33.D. CD7 versus cyMPOA BC D

A case report of acute panmyelosis with myelofibRosis (APMF) with a distinct molecular pattern

https://biblio.ugent.be/publication/8600023/file/8623234.pdf

A case report of acute panmyelosis with myelofibRosis (APMF) with a distinct molecular pattern

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