Chromosomal translocations involving 9p24/JAK2 are rare genetic events, typically occurring in B-cell acute lymphoblastic leukaemias (ALL) and in myeloid/lymphoid neoplasms with JAK2 rearrangement (M/LN-JAK2).1 2 The latter are rare and heterogeneous haematopoietic stem cell (HSC) disorders, belonging to the spectrum of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions (M/LN-eo-TK).1 2

M/LN-JAK2 mostly affects adult males (male-to-female ratio: 3.7) with the mean age at diagnosis of 52.8 years (range: 12–86) (table 1; online supplemental table 1). Clinically, they disclose myeloproliferative (MPN) or myelodysplastic/myeloproliferative (MDS/MPN) features, variable peripheral blood (PB) eosinophilia, hepatosplenomegaly and/or lymphadenopathies.3 4 A minority of cases present with (or progress to) acute myeloid leukaemia (AML) and ALL.4 Bone marrow (BM) studies show high cellularity, variable expansion of immature erythroid precursors, tissue eosinophilia and variable interstitial fibrosis.4 Most cases harbour t(8;9)(p22;p24)/PCM1::JAK2, but t(9;22)(p24;q11.2)/BCR::JAK2 and t(9;12)(p24;p13)/ETV6::JAK2 have been reported as well.3 5 6 These are currently regarded as genetic variants of M/LN-JAK2 and share several clinical and laboratory features with t(8;9)(p22;p24)/PCM1::JAK2 cases.3 4 6 A small subset of cases discloses alternative fusion partners and has clinical features only partially consistent with M/LN-eo-TK.3 7 Disease course is variable, spanning from indolent (cases with MPN-like features) to aggressive (cases with AML/ALL presentation). The median overall survival without transplant is <24 months.8

[jcp-2024-209587supp001.pdf]

Summary of clinical and genetic features of published JAK2-rearranged myeloid neoplasms based on fusion partners and clinical presentation

Whether JAK2-rearranged myeloid neoplasms with features other than MPN and MDS/MPN belong to the spectrum of M/LN-JAK2 is still a matter of debate. Little is also known about the best way of classifying and diagnosing cases with JAK2 fusion partners other than PCM1, BCR and ETV6 …