JAK2 V617F 양성 급성골수성백혈병의 임상병리학적 특징 2예
JAK2 V617F-Positive Acute Myeloid Leukemia: Clinicopathological Features of Two Cases
서울대학교 의과대학 검사의학교실1, 분당서울대학교병원 내과2, 분당서울대학교병원 진단검사의학과3
Department of Laboratory Medicine1, Seoul National University College of Medicine, Seoul; Department of Internal Medicine2, Seoul National University Bundang Hospital, Seongnam; Department of Laboratory Medicine3, Seoul National University Bundang Hospital, Seongnam, KoreaCorrespondence to:
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Lab Med Online 2022; 12(1): 53-57
Published January 1, 2022
Copyright © The Korean Society for Laboratory Medicine.
1. Patient 1
A 37-year-old male patient visited Seoul National University Bundang Hospital for further evaluation of pancytopenia. His complete blood count (CBC) revealed a hemoglobin concentration of 79 g/L, an absolute neutrophil count of 523×106/L, and a platelet count of 69×109/L. Peripheral blood smear showed 26% blasts. Subsequently, BM biopsy was performed, which revealed an increase in myeloblasts positive for CD13, CD33, CD34, CD38 (partial), CD117, HLA-DR, and CD123, as confirmed with flow cytometry. Furthermore, the results revealed hypercellular marrow with dysmegakaryopoietic features such as monolobation, micromegakaryocytes (Fig. 1A), and grade 2 reticulin fibrosis (Fig. 1B). The initial cytogenetic study showed no mitosis. However, the fluorescence
Figure 1. Morphological features of the bone marrow from patients with AML carrying the
JAK2V617F mutation. (A) Patient 1: Micromegakaryocytes (hematoxylin-eosin, 400×). (B) Patient 1: diffuse reticulin fibrosis (MF-2) (reticulin, 400×). (C) Patient 2: Hypolobated, dysplastic megakaryocytes (hematoxylin-eosin, 400×). (D) Patient 2: diffuse reticulin fibrosis (MF-2) (reticulin, 200×).
Figure 2. IGV browser visualization of the NGS results. (A) Patient 1: NM_004972.3(JAK2):c.1849G>T (p.Val617Phe) in the
JAK2gene. (B) Patient 1: NM_005373.2(MPL):c.1543T>A (p.Trp515Arg) in the MPLgene. (C) Patient 1: NM_005089.3(ZRSR2):c.1093_1103del (p.Glu365Profs*16) in the ZRSR2gene. (D) Patient 2: NM_004972.3(JAK2):c.1849G>T (p.Val617Phe) in the JAK2gene. (E) Patient 2: NM_005475.2(SH2B3):c.1009dup (p.Ser337Phefs*3) in the SH2B3gene.
Figure 3. Morphological features of the bone marrow from patient 1 after stem cell transplantation (SCT). (A) BM biopsy after 1st SCT (CD61, 400×). (B) BM biopsy after 2nd SCT (hematoxylin-eosin, 400×). Micromegakaryocytes could be occasionally observed in a small cellular area.
2. Patient 2
A 47-year-old male patient with dysarthria was admitted to the neurology department of Seoul National University Bundang Hospital. He had never been diagnosed with hematologic disorders or cancer. Severe left middle cerebral artery stenosis and multifocal territories embolic infarction were confirmed with brain magnetic resonance imaging. The CBC profile of the patient revealed a hemoglobin concentration of 136 g/L, an absolute neutrophil count of 2,320×106/L, and a platelet count of 183×109/L, indicating no cytopenia but presence of more than 20% peripheral blasts. Next, BM biopsy was performed, which revealed an increase in myeloblasts positive for CD13, CD33, CD34, CD117 (partial), HLA-DR, and myeloperoxidase (partial), as confirmed with flow cytometry. Additionally, normocellular marrow with dysmegakaryopoietic features, such as widely separate nuclei and monolobation (Fig. 1C), and grade 2 reticulin fibrosis (Fig. 1D) were also observed. The initial cytogenetic study indicated a normal karyotype. Based on these findings, a diagnosis of AML, not otherwise specified was made. The NGS analysis identified
The valine-to-phenylalanine substitution at codon 617 in the
In this case report, we presented two cases of
Conflicts of Interest
- Swerdlow SH, Campo E, et al, eds. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon, France: 2017:39-53.
- Steensma DP, McClure RF, Karp JE, Tefferi A, Lasho TL, Powell HL, et al.
JAK2V617F is a rare finding in de novoacute myeloid leukemia, but STAT3 activation is common and remains unexplained. Leukemia 2006;20:971-8.
- Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS, et al. The
JAK2V617F mutation in de novo acute myelogenous leukemias. Oncogene 2006;25:1434-6.
- Hidalgo- López JE, Kanagal-Shamanna R, L. Medeiros LJ, Estrov Z, Yin CC, Verstovsek S, et al. Morphologic and molecular characteristics of de novo AML with
JAK2V617F mutation. J Natl Compr Canc Netw 2017;15:790-6.
- Aynardi J, Manur R, Hess PR, Chekol S, Morrissette JJD, Babushok D, et al.
JAK2V617F-positive acute myeloid leukemia (AML): a comparison between de novo AML and secondary AML transformed from an underlying myeloproliferative neoplasm. A study from the Bone Marrow Pathology Group. Br J Haematol 2018;182:78-85.
- De Roeck L, Michaux L, Debackere K, Lierman E, Vandenberghe P, Devos T. Coexisting driver mutations in MPN: clinical and molecular characteristics of a series of 11 patients. Hematology 2018;23:785-92.
- Jang MA, Seo MY, Choi KJ, Hong DS. A rare case of essential thrombocythemia with coexisting
JAK2and MPLdriver mutations. J Korean Med Sci 2020;35:e168.
- Defour JP, Chachoua I, Pecquet C, Constantinescu SN. Oncogenic activation of MPL/thrombopoietin receptor by 17 mutations at W515: implications for myeloproliferative neoplasms. Leukemia 2016;30:1214-6.
- Mansier O, Luque Paz D, Ianotto JC, Le Bris Y, Chauveau A, Boyer F, et al. Clinical and biological characterization of MPN patients harboring two driver mutations, a French intergroup of myeloproliferative neoplasms (FIM) study. Am J Hematol 2018;93:E84-6.