TY - JOUR
T1 - The detection of SRSF2 mutations in routinely processed bone marrow biopsies is useful in the diagnosis of chronic myelomonocytic leukemia
AU - Federmann, Birgit
AU - Abele, Manuel
AU - Rosero Cuesta, David Santiago
AU - Vogel, Wichard
AU - Boiocchi, Leonardo
AU - Kanz, Lothar
AU - Quintanilla-Martinez, Leticia
AU - Orazi, Attilio
AU - Bonzheim, Irina
AU - Fend, Falko
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Diagnosis of chronic myelomonocytic leukemia (CMML) is based on a combination of clinical, laboratory, and morphological parameters, including persistent peripheral blood monocytosis. Recently, mutations of serine/arginine-rich splicing factor 2 (SRSF2) have been identified in 40% to 50% of CMMLs and occasionally in other myeloid disorders. In this study, we established a robust assay for the detection of SRSF2 mutations in decalcified, paraffin-embedded bone marrow (BM) biopsies and investigated its diagnostic utility. BM biopsies of 78 patients with myeloid neoplasms, including 36 CMMLs, 22 myelodysplastic syndromes (MDS), and 20 Ph- myeloproliferative neoplasms (MPN) were analyzed. The region around hot spot P95 in exon 1 of SRSF2 was amplified and bidirectionally sequenced. In addition, a restriction fragment length polymorphism analysis was established. The JAK2 V617F mutation was investigated by allele-specific polymerase chain reaction. SRSF2 mutations were identified in 16 (44%) of 36 CMMLs, including 1 of 3 cases with associated systemic mastocytosis, 4 (20%) of 20 Ph- MPN, and 1 (4.5%) of 22 MDS. Restriction fragment length polymorphism analysis detected all mutations with the exception of a single P95A. Of note, 2 cases of JAK2 V617F+ primary myelofibrosis with SRSF2 mutation initially were diagnosed as CMML based on significant peripheral blood monocytosis. In CMML, no correlation with histopathology and/or clinical parameters was observed, but SRSF2 mutations were associated with normal karyotype (P
AB - Diagnosis of chronic myelomonocytic leukemia (CMML) is based on a combination of clinical, laboratory, and morphological parameters, including persistent peripheral blood monocytosis. Recently, mutations of serine/arginine-rich splicing factor 2 (SRSF2) have been identified in 40% to 50% of CMMLs and occasionally in other myeloid disorders. In this study, we established a robust assay for the detection of SRSF2 mutations in decalcified, paraffin-embedded bone marrow (BM) biopsies and investigated its diagnostic utility. BM biopsies of 78 patients with myeloid neoplasms, including 36 CMMLs, 22 myelodysplastic syndromes (MDS), and 20 Ph- myeloproliferative neoplasms (MPN) were analyzed. The region around hot spot P95 in exon 1 of SRSF2 was amplified and bidirectionally sequenced. In addition, a restriction fragment length polymorphism analysis was established. The JAK2 V617F mutation was investigated by allele-specific polymerase chain reaction. SRSF2 mutations were identified in 16 (44%) of 36 CMMLs, including 1 of 3 cases with associated systemic mastocytosis, 4 (20%) of 20 Ph- MPN, and 1 (4.5%) of 22 MDS. Restriction fragment length polymorphism analysis detected all mutations with the exception of a single P95A. Of note, 2 cases of JAK2 V617F+ primary myelofibrosis with SRSF2 mutation initially were diagnosed as CMML based on significant peripheral blood monocytosis. In CMML, no correlation with histopathology and/or clinical parameters was observed, but SRSF2 mutations were associated with normal karyotype (P
KW - Bone marrow biopsy
KW - Chronic myelomonocytic leukemia
KW - JAK2 mutation
KW - Myeloproliferative neoplasms
KW - SRSF2 mutation
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U2 - 10.1016/j.humpath.2014.08.014
DO - 10.1016/j.humpath.2014.08.014
M3 - Article
C2 - 25305095
AN - SCOPUS:84912535552
VL - 45
SP - 2471
EP - 2479
JO - Human Pathology
JF - Human Pathology
SN - 0046-8177
IS - 12
ER -