TY - JOUR
T1 - Utility of JAK2 V617F allelic burden in distinguishing chronic myelomonocytic Leukemia from Primary myelofibrosis with monocytosis
AU - Hu, Zhihong
AU - Ramos, Carlos E.Bueso
AU - Medeiros, L. Jeffrey
AU - Zhao, Chong
AU - Yin, C. Cameron
AU - Li, Shaoying
AU - Hu, Shimin
AU - Wang, Wei
AU - Thakral, Beenu
AU - Xu, Jie
AU - Verstovsek, Srdan
AU - Lin, Pei
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2019/3
Y1 - 2019/3
N2 - The concurrent presence of JAK2 V617F, monocytosis, and bone marrow fibrosis can be observed in both chronic myelomonocytic leukemia (CMML) and primary myelofibrosis (PMF). It can be challenging to distinguish CMML with JAK2 mutation and fibrosis from other myeloid neoplasms, particularly PMF. To identify key features that may help distinguish these 2 entities, we retrospectively studied 21 cases diagnosed as “CMML” with JAK2 V617F and bone marrow fibrosis that were identified from a cohort of 610 cases of CMML diagnosed in 2006 to 2016. Upon further review, we confirmed the diagnosis of CMML in 7 cases, 11 cases were reclassified as PMF, and 3 cases had features intermediate between CMML and PMF (gray zone). These 11 cases of PMF with monocytosis featured a higher JAK2 V617F allelic burden (median, 43%; range, 20%-62%) and atypical pleomorphic megakaryocytes with hyperchromatic nuclei. Complete blood count showed more pronounced myeloid left shift. In contrast, 7 CMML cases had significantly lower JAK2 V617F allelic burden (median, 17%; range, 5%-36%; P <.0001) and dysplastic megakaryocytes along with variable degree of dysplasia in other lineages. The median survival of PMF and CMML patients was 32 and 40 months, respectively. We conclude that besides morphology of megakaryocytes and other features, JAK2 V617F allelic burden can help differentiate CMML from PMF with monocytosis. SRSF2 and RAS mutations are observed in both disease categories. Rare gray-zone cases exist with hybrid features.
AB - The concurrent presence of JAK2 V617F, monocytosis, and bone marrow fibrosis can be observed in both chronic myelomonocytic leukemia (CMML) and primary myelofibrosis (PMF). It can be challenging to distinguish CMML with JAK2 mutation and fibrosis from other myeloid neoplasms, particularly PMF. To identify key features that may help distinguish these 2 entities, we retrospectively studied 21 cases diagnosed as “CMML” with JAK2 V617F and bone marrow fibrosis that were identified from a cohort of 610 cases of CMML diagnosed in 2006 to 2016. Upon further review, we confirmed the diagnosis of CMML in 7 cases, 11 cases were reclassified as PMF, and 3 cases had features intermediate between CMML and PMF (gray zone). These 11 cases of PMF with monocytosis featured a higher JAK2 V617F allelic burden (median, 43%; range, 20%-62%) and atypical pleomorphic megakaryocytes with hyperchromatic nuclei. Complete blood count showed more pronounced myeloid left shift. In contrast, 7 CMML cases had significantly lower JAK2 V617F allelic burden (median, 17%; range, 5%-36%; P <.0001) and dysplastic megakaryocytes along with variable degree of dysplasia in other lineages. The median survival of PMF and CMML patients was 32 and 40 months, respectively. We conclude that besides morphology of megakaryocytes and other features, JAK2 V617F allelic burden can help differentiate CMML from PMF with monocytosis. SRSF2 and RAS mutations are observed in both disease categories. Rare gray-zone cases exist with hybrid features.
KW - Chronic myelomonocytic leukemia
KW - Gray zone
KW - JAK2V617F
KW - Monoctyosis
KW - Primary myelofibrosis
KW - SRSF2 mutation
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U2 - 10.1016/j.humpath.2018.10.026
DO - 10.1016/j.humpath.2018.10.026
M3 - Article
C2 - 30447300
AN - SCOPUS:85062065415
SN - 0046-8177
VL - 85
SP - 290
EP - 298
JO - Human Pathology
JF - Human Pathology
ER -