Clinicopathologic characteristics, genetic features, and treatment options for acute lymphoblastic leukemia with JAK2 rearrangement-A 10-case study and literature review

Hum Pathol. 2023 Jun:136:1-15. doi: 10.1016/j.humpath.2023.03.002. Epub 2023 Mar 22.


JAK2 rearrangement (JAK2-R) in acute lymphoblastic leukemia (ALL) is rare and often categorized as B-ALL with BCR::ABL1-like features based on the World Health Organization classification. We report 10 patients with JAK2-R ALL, 9 males and 1 female, with a median age 40.5 years. Eight patients presented with marked leukocytosis (median WBC, 63 × 10 9/L) and hypercellular (>95%) bone marrow with increased lymphoblasts (72%-95%). There was no evidence of bone marrow fibrosis or hypereosinophilia. Immunophenotypic analysis showed 9 B-cell and 1 T-cell neoplasms. Using fluorescence in situ hybridization (FISH) and RNA sequencing analysis, JAK2 partners were identified for 7 cases and included PCM1 (n = 4), ETV6 (n = 2) and BCR (n = 1). All patients received upfront polychemotherapy. Additionally, 2 patients received ruxolitinib, 2 received allogeneic stem cell transplant, and 1 received CAR-T therapy. The 1- and 3-year overall survival rates were 55.6% and 22.2%, respectively. A literature review identified 24 B-ALL and 4 T-ALL cases with JAK2-R reported, including 16 males, 6 females and 6 gender not stated. Many JAK2 partner-genes were reported with the most common being PAX5 (n = 7), ETV6 (n = 5), BCR (n = 4) and PCM1 (n = 2). Survival data on 13 reported cases showed 1- and 3-year overall survival rates of 41.7% and 41.7%, respectively. In summary, JAK2-R ALL occurs more often in adult males, are mostly of B-cell lineage, and associated with an aggressive clinical course. Absence of eosinophilia and bone marrow fibrosis and no evidence of preexisting/concurrent JAK2-R myeloid neoplasms distinguish JAK2-R ALL from other myeloid/lymphoid neoplasms with eosinophilia and JAK2-R.

Keywords: Acute lymphoblastic leukemia; JAK2 rearrangement; Myeloid/lymphoid neoplasm with eosinophilia and tyrosine kinase gene rearrangement; Ruxolitinib; Stem cell transplant.

Publication types

  • Review

MeSH terms

  • Eosinophilia* / pathology
  • Female
  • Humans
  • In Situ Hybridization, Fluorescence
  • Janus Kinase 2 / genetics
  • Male
  • Oncogene Proteins, Fusion / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma* / therapy
  • Primary Myelofibrosis*


  • Oncogene Proteins, Fusion
  • JAK2 protein, human
  • Janus Kinase 2