Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study

• Published in: Modern pathology 2019-04, Vol.32 (4), p.490-498
• Main Authors: Tang, Guilin, Sydney Sir Philip, John Kennedy, Weinberg, Olga, Tam, Wayne, Sadigh, Sam, Lake, Jonathan I., Margolskee, Elizabeth M., Rogers, Heesun J., Miranda, Roberto N., Bueso-Ramos C, Carlos, Hsi, Eric D., Orazi, Attilio, Hasserjian, Robert P., Arber, Daniel A., Bagg, Adam, Wang, Sa A.
• Format: Article
• Language: English
• Subjects: 38/32; 631/67/1990/2331; 692/420/2489/68; Adult; BCR-ABL protein; Blood cancer; Bone marrow; Chromosomes, Human, Pair 9 - genetics; Eosinophilia; Erythroblasts; Female; Gene Rearrangement; Hematologic Neoplasms - genetics; Humans; Janus kinase 2; Janus Kinase 2 - genetics; Laboratory Medicine; Lymphatic leukemia; Male; Medicine; Medicine & Public Health; Middle Aged; Myelodysplastic syndrome; Myelofibrosis; Oncogene Proteins, Fusion - genetics; Pathology; Translocation; Tumors
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-018-0165-9

The purpose of this study is to examine hematopoietic neoplasms with 9p24/ JAK2 rearrangement including neoplasms associated with t(8;9)(p22;p24)/ PCM1-JAK2 fusion neoplasm as well as cases with translocations involving 9p24/ JAK2 and other partner genes. From seven large medical centers, we identified ten patients with t(8;9)(p22;p24) / PCM1-JAK2 and 3 with t(9p24;v)/ JAK2 at diagnosis. Majority of the cases showed myeloproliferative neoplasm (MPN) associated features ( n  = 7) characterized by variable degrees of eosinophilia, myelofibrosis, frequent proliferations of early erythroblasts in bone marrow and extramedullary sites, and infrequent/absent somatic mutations. Other less common presentations included myelodysplastic syndromes (MDS) or MDS/MPN (one each). Four patients presented with B-lymphoblastic leukemia (B-ALL), and of them, two patients with t(8;9)(p22;p24.1) were proven to be B-lymphoblastic crisis of MPN; and the other two cases with t(9p24;v) both were de novo B-ALL, BCR-ABL1 -like (Ph-like). We show that the hematopoietic neoplasms with 9p24/ JAK2 rearrangement are extremely rare, and most of them are associated with t(8;9)(p22;p24)/ PCM1-JAK2 , a recent provisional World Health Organization entity under “myeloid/lymphoid neoplasm with a specific gene rearrangement”. Cases of t(8;9)(p22;p24)/ PCM1-JAK2 , though heterogeneous, do exhibit some common clinicopathological characteristic features. Cases with t(9p24;v)/ JAK2 are extremely rare; while such cases with a MPN presentation may resemble t(8;9)(p22;p24.1)/ PCM1-JAK2 , B-ALL cases presenting de novo B-ALL might belong to Ph-like B-ALL.