Janus kinase 2 V617F mutation is detectable in spleen of patients with chronic myeloproliferative diseases suggesting a malignant nature of splenic extramedullary hematopoiesis

• Published in: Human pathology 2007-12, Vol.38 (12), p.1760-1763
• Main Authors: Konoplev, Sergej, MD, PhD, Hsieh, Pin-Pen, MD, Chang, Chung-Che, MD, PhD, Medeiros, L. Jeffrey, MD, Lin, Pei, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Biological and medical sciences; Bone Marrow - physiopathology; Chromosome Aberrations; Chronic myelomonocytic leukemia; Chronic myeloproliferative disorders; Extramedullary hematopoiesis; Female; Hematologic and hematopoietic diseases; Hematopoiesis, Extramedullary; Humans; Investigative techniques, diagnostic techniques (general aspects); JAK2; Janus Kinase 2 - genetics; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Middle Aged; Mutation; Myeloproliferative Disorders - genetics; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reverse Transcriptase Polymerase Chain Reaction; Spleen; Spleen - physiopathology
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2007.04.004

Summary Extramedullary hematopoiesis occurs in patients with a variety of hematologic diseases, and the spleen is a common site. Extramedullary hematopoiesis is very common in chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The pathogenesis of extramedullary hematopoiesis is unknown. Using JAK2 V617F mutation as a molecular marker, we assessed paired spleen and bone marrow samples of 15 patients with various types of chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases. The diagnosis was chronic idiopathic myelofibrosis (n = 8), polycythemia vera (n = 3), and chronic myelomonocytic leukemia (n = 4). DNA was extracted from fixed, paraffin-embedded tissue and assessed for JAK2 V617F by real-time polymerase chain reaction assay followed by melting curve analysis. Concordant JAK2 mutation was detected in the paired samples in 7 patients. A discordant result with JAK2 V617F found in the spleen but not bone marrow was noted in 1 patient. These results indicate that extramedullary hematopoiesis in patients with chronic myeloproliferative diseases and myeloproliferative/myelodysplastic diseases is a clonal process and lend support to the theory that the cells of extramedullary hematopoiesis are carried from the bone marrow.