BCR–JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia

He, Rong; Greipp, Patricia T.; Rangan, Aruna; Mai, Ming; Chen, Dong; Reichard, Kaaren K.; Nelsen, Laura; Pardanani, Animesh; Hanson, Curtis A.; Viswanatha, David S.

doi:10.1016/j.cancergen.2016.03.002

Cited by 19 publications

(10 citation statements)

References 27 publications

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“…[70][71][72][73][74] To date, murine models have only been established for ETV6-JAK2, which showed the induction of a fatal mixed myeloand/or T-cell lymphoproliferative disorder and potential susceptibility to JAK inhibitors. 75,76 The phenotype and clinical course of JAK2-rearranged patients resemble leukemias associated with other TK fusion genes (eg, BCR-ABL1-positive CML/ALL), rather than classical Philadelphiachromosome-negative MPNs with the JAK2 V617F mutation.…”

Section: Jak2 Fusion Genesmentioning

confidence: 99%

Myeloid neoplasms with eosinophilia

Reiter

Gotlib

2017

Blood

222

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Molecular diagnostics has generated substantial dividends in dissecting the genetic basis of myeloid neoplasms with eosinophilia. The family of diseases generated by dysregulated fusion tyrosine kinase (TK) genes is recognized by the World Health Organization (WHO) category, “Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2.” In addition to myeloproliferative neoplasms (MPN), these patients can present with myelodysplastic syndrome/MPN, as well as de novo or secondary mixed-phenotype leukemias or lymphomas. Eosinophilia is a common, but not invariable, feature of these diseases. The natural history of PDGFRA- and PDGFRB-rearranged neoplasms has been dramatically altered by imatinib. In contrast, patients with FGFR1 and JAK2 fusion TK genes exhibit a more aggressive course and variable sensitivity to current TK inhibitors, and in most cases, long-term disease-free survival may only be achievable with allogeneic hematopoietic stem cell transplantation. Similar poor prognosis outcomes may be observed with rearrangements of FLT3 or ABL1 (eg, both of which commonly partner with ETV6), and further investigation is needed to validate their inclusion in the current WHO-defined group of eosinophilia-associated TK fusion-driven neoplasms. The diagnosis chronic eosinophilic leukemia, not otherwise specified (CEL, NOS) is assigned to patients with MPN with eosinophilia and nonspecific cytogenetic/molecular abnormalities and/or increased myeloblasts. Myeloid mutation panels have identified somatic variants in patients with a provisional diagnosis of hypereosinophilia of undetermined significance, reclassifying some of these cases as eosinophilia-associated neoplasms. Looking forward, one of the many challenges will be how to use the results of molecular profiling to guide prognosis and selection of actionable therapeutic targets.

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Section: Jak2 Fusion Genesmentioning

confidence: 99%

Myeloid neoplasms with eosinophilia

Reiter

Gotlib

2017

Blood

222

274

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“…With censoring for allo SCT, OS was not different for patients treated with or without ruxolitinib (Figure 2). An allo SCT was performed in 18/49 (37%) patients 8,31‐33,36‐38,42,46,49,50,52,56 . Two further patients underwent an autologous SCT (auto SCT) after intensive chemotherapy for ALL 33,56 .…”

Section: Resultsmentioning

confidence: 99%

“…We therefore sought to evaluate the clinical characteristics and response to various TKI in 18 patients with myeloid neoplasms and associated PCM1‐JAK2 , BCR‐JAK2 or ETV6‐ABL1 fusion genes. In an extended analysis, we integrated our data into the reports of 40 patients with JAK2 fusion genes ( PCM1‐JAK2 , n = 28) 8,9,12‐15,28‐40 or BCR‐JAK2 (n = 12) 41‐52 and 14 patients with TKI‐treated ETV6‐ABL1 positive chronic myeloid neoplasms 16‐27,53,54 . This analysis provides a comprehensive overview of responses to TKIs in patients with these rare fusions.…”

Section: Introductionmentioning

confidence: 99%

Response to tyrosine kinase inhibitors in myeloid neoplasms associated with PCM1‐JAK2, BCR‐JAK2 and ETV6‐ABL1 fusion genes

et al. 2020

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We report on 18 patients with myeloid neoplasms and associated tyrosine kinase (TK) fusion genes on treatment with the TK inhibitors (TKI) ruxolitinib (PCM1‐JAK2, n = 8; BCR‐JAK2, n = 1) and imatinib, nilotinib or dasatinib (ETV6‐ABL1, n = 9). On ruxolitinib (median 24 months, range 2‐36 months), a complete hematologic response (CHR) and complete cytogenetic response (CCR) was achieved by five of nine and two of nine patients, respectively. However, ruxolitinib was stopped in eight of nine patients because of primary resistance (n = 3), progression (n = 3) or planned allogeneic stem cell transplantation (allo SCT, n = 2). At a median of 36 months (range 4‐78 months) from diagnosis, five of nine patients are alive: four of six patients after allo SCT and one patient who remains on ruxolitinib. In ETV6‐ABL1 positive patients, a durable CHR was achieved by four of nine patients (imatinib with one of five, nilotinib with two of three, dasatinib with one of one). Because of inadequate efficacy (lack of hematological and/or cytogenetic/molecular response), six of nine patients (imatinib, n = 5; nilotinib, n = 1) were switched to nilotinib or dasatinib. At a median of 23 months (range 3‐60 months) from diagnosis, five of nine patients are in CCR or complete molecular response (nilotinib, n = 2; dasatinib, n = 2; allo SCT, n = 1) while two of nine patients have died. We conclude that (a) responses on ruxolitinib may only be transient in the majority of JAK2 fusion gene positive patients with allo SCT being an important early treatment option, and (b) nilotinib or dasatinib may be more effective than imatinib to induce durable complete remissions in ETV6‐ABL1 positive patients.

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“…6,10,54-56 ETV6-JAK2 [t(9;12)(p24; p13)] and BCR-JAK2 [t(9;22)(p24;q11)] are the other fusion genes reported only in few patients. 6,10,[57][58][59] As with other fusion gene rearrangements resulting from a translocation, conventional cytogenetics to identify t(8;9) followed by confirmatory FISH with JAK2 break-apart probes is recommended to confirm the diagnosis. 6,10 MLN-Eo With FLT3 or ABL1 Rearrangement ETV6-FLT3 resulting from t(12;13)(p13;q12) and ETV6-ABL1 resulting from t(9;12)(q34;p13) are the common fusion genes involved in the majority of cases.…”

Section: Cytogenetic and Molecular Testingmentioning

confidence: 99%

Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology

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Bose

et al. 2020

Journal of the National Comprehensive Cancer Network

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Eosinophilic disorders and related syndromes represent a heterogeneous group of neoplastic and nonneoplastic conditions, characterized by more eosinophils in the peripheral blood, and may involve eosinophil-induced organ damage. In the WHO classification of myeloid and lymphoid neoplasms, eosinophilic disorders characterized by dysregulated tyrosine kinase (TK) fusion genes are recognized as a new category termed, myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB or FGFR1 or with PCM1-JAK2. In addition to these aforementioned TK fusion genes, rearrangements involving FLT3 and ABL1 genes have also been described. These new NCCN Guidelines include recommendations for the diagnosis, staging, and treatment of any one of the myeloid/lymphoid neoplasms with eosinophilia (MLN-Eo) and a TK fusion gene included in the 2017 WHO Classification, as well as MLN-Eo and a FLT3 or ABL1 rearrangement.

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BCR–JAK2 fusion in a myeloproliferative neoplasm with associated eosinophilia

Cited by 19 publications

References 27 publications

Myeloid neoplasms with eosinophilia

Myeloid neoplasms with eosinophilia

Response to tyrosine kinase inhibitors in myeloid neoplasms associated with PCM1‐JAK2, BCR‐JAK2 and ETV6‐ABL1 fusion genes

Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology

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