Suknuntha Kran, Geyer Julia T, Patel Keyur Pravinchandra, Weinberg Olga K, Rogers Heesun J, Lake Jonathan I, Lauridsen Luke, Patel Jay L, Kluk Michael J, Arber Daniel A, Hsi Eric D, Bagg Adam, Bueso-Ramos Carlos, Orazi Attilio
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, United States; Chakri Naruebodindra Medical Institute, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Samut Prakan 10540, Thailand.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, United States.
Leuk Res. 2023 Apr;127:107033. doi: 10.1016/j.leukres.2023.107033. Epub 2023 Feb 8.
The presence of JAK2 exon 12 mutation was included by the 2016 World Health Organization (WHO) Classification as one of the major criteria for diagnosing polycythemia vera (PV). Few studies have evaluated the clinical presentation and bone marrow morphology of these patients and it is unclear if these patients fulfill the newly published criteria of 5th edition WHO or The International Consensus Classification (ICC) criteria for PV. Forty-three patients with JAK2 exon 12 mutations were identified from the files of 7 large academic institutions. Twenty patients had complete CBC and BM data at disease onset. Fourteen patients met the diagnostic criteria for PV and the remaining six patients were diagnosed as MPN-U. At diagnosis, 9/14 patients had normal WBC and platelet counts (isolated erythrocytosis/IE subset); while 5/14 had elevated WBC and/or platelets (polycythemic /P subset). We found that hemoglobin and hematocrit tended to be lower in the polycythemia group. Regardless of presentation (P vs IE), JAK2 deletion commonly occurred in amino acids 541-544 (62 %). MPN-U patients carried JAK2 exon 12 mutation, but did not fulfill the criteria for PV. Half of the patients had hemoglobin/hematocrit below the diagnostic threshold for PV, but showed increased red blood cell count with low mean corpuscular volume (56-60 fL). Three cases lacked evidence of bone marrow hypercellularity. In summary, the future diagnostic criteria for PV may require a modification to account for the variant CBC and BM findings in some patients with JAK2 exon 12 mutation.
JAK2外显子12突变的存在被2016年世界卫生组织（WHO）分类纳入真性红细胞增多症（PV）诊断的主要标准之一。很少有研究评估这些患者的临床表现和骨髓形态，并且尚不清楚这些患者是否符合WHO第五版或国际共识分类（ICC）的PV新发布标准。从7家大型学术机构的档案中识别出43例JAK2外显子12突变患者。20例患者在疾病发作时有完整的全血细胞计数（CBC）和骨髓（BM）数据。14例患者符合PV诊断标准，其余6例患者被诊断为未分类的骨髓增殖性肿瘤（MPN-U）。诊断时，14例患者中有9例白细胞和血小板计数正常（单纯红细胞增多症/IE亚组）；而14例中有5例白细胞和/或血小板升高（红细胞增多症/P亚组）。我们发现红细胞增多症组的血红蛋白和血细胞比容往往较低。无论表现形式（P组与IE组）如何，JAK2缺失常见于氨基酸541 - 544（62%）。MPN-U患者携带JAK2外显子12突变，但不符合PV标准。一半的患者血红蛋白/血细胞比容低于PV诊断阈值，但红细胞计数增加，平均红细胞体积较低（56 - 60 fL）。3例缺乏骨髓细胞增多的证据。总之，PV未来的诊断标准可能需要修改，以考虑一些JAK2外显子12突变患者中不同的CBC和BM表现。
