t(8;9)(p22;p24) PCM1/JAK2
2006-09-01 Andreas Reiter , Christoph Walz Affiliation1.Medizinische Universitatsklinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany
Clinics and Pathology
Disease
The PCM1-JAK2 resulting from a t(8;9)(p22;p24) fusion gene occurs in both myeloid and lymphoid malignancies: CML-like chronic phase disease with associated eosinophilia and marrow fibrosis and possible evolvement to secondary AML and B-ALL (blast crisis), de novo B-ALL and T-ALL/T-NHL. Striking male predominance.
Phenotype stem cell origin
Atypical chronic myeloid leukemia; chronic eosinophilic leukemia; pre-B-cell acute lymphoblastic leukemia; acute myeloid leukemia M6;T-cell acute lymphoid leukemia; myelodysplastic syndrome/myeloproliferative disease, unclassifiable; secondary acute myeloid leukemia.
Epidemiology
15 published cases (plus 3 unpublished), striking male predominance, only 2 females, median age 45.5 years (range, 12-74).
Clinics
CML-like chronic phase disease with associated eosinophilia and marrow fibrosis and possible evolvement to secondary AML and B-ALL (blast crisis), de novo B-ALL and T-ALL/T-NHL. Striking male predominance, clinical course highly variable.
Treatment
Allogeneic stem cell transplantation; interferon; hydroxyurea; no specific JAK2 inhibitor currently available.
Prognosis
PCM1-JAK2 positive disease is an aggressive disease compared to patients with MPD and associated V617F JAK2 mutation. Acute leukemias (de novo and secondary) seen in approximately 50% of all cases.
Cytogenetics
Figure 1. left: FISH: JAK2 breakapart probe. The der(8) is marked by the red 5JAK2 signal and the der(9) by the green 3JAK2 signal - Courtesy Marc Muller; center top: Ideogram and t(8;9)(p22;p24) QFQ-banding - Courtesy Marc Muller; center bottom: cytology - Courtesy Lucienne Michaux, Peter Meeus and Peter Vandenberghe; right: t(8;9)(p22;24) PCM1/JAK2 R-banding and FISH- Courtesy Lucienne Michaux, Peter Meeus and Peter Vandenberghe
Genes Involved and Proteins
Gene name
PCM1 (pericentriolar material 1)
Location
8p22
Dna rna description
41 exons; alternate splicing.
Protein description
PCM1 is involved in recruiting proteins necessary for centrosome replication and predicted to contain multiple coiled-coil motifs.
Gene name
JAK2 (janus kinase 2)
Location
9p24.1
Dna rna description
23 exons.
Protein description
JAK2 is a tyrosine-protein kinase with transmembrane and tyrosine kinase domains.
Result of the Chromosomal Anomaly
Description
5 PCM1 - 3 JAK2.
Transcript
PCM1-JAK2 chimeric RNA constantly present; variable positions of the breakpoints within PCM1 and JAK2; reciprocal transcript may be present.
Diagrammatic representation of normal JAK2, normal PCM1 and the PCM1-JAK2 fusion protein.
Description
PCM1-JAK2 mRNA is predicted to encode a protein that retains several of the predicted coiled-coil domains from PCM1 and the entire tyrosine kinase domain of JAK2.
Oncogenesis
As has been found for other tyrosine kinase fusion proteins, e.g. BCR-ABL, it is likely that one or more of the coiled-coil motifs from PCM1 result in dimerization or oligomerization of the PCM1-JAK2 chimera, with consequent constitutive activation of the JAK2 kinase domain.
Highly cited references
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34298741 | 2021 | Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics. | 165 |
| 35472244 | 2022 | PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Neoplasia: A Systematic Review of the Clinical Literature. | 58 |
| 23372669 | 2013 | t(8;9)(p22;p24)/PCM1-JAK2 activates SOCS2 and SOCS3 via STAT5. | 50 |
| 34205834 | 2021 | T-Cell Lymphoblastic Lymphoma Arising in the Setting of Myeloid/Lymphoid Neoplasms with Eosinophilia: LMO2 Immunohistochemistry as a Potentially Useful Diagnostic Marker. | 36 |
| 34707996 | 2021 | Diagnosis and Treatment of Myeloproliferative Neoplasms With PCM1-JAK2 Rearrangement: Case Report and Literature Review. | 34 |
| 38493200 | 2024 | Application of droplet digital PCR in minimal residual disease monitoring of rare fusion transcripts and mutations in haematological malignancies. | 34 |
| 29025601 | 2017 | A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia. | 28 |
| 32238402 | 2020 | The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia. | 25 |
| 39980500 | 2025 | A Case of Myeloproliferative Neoplasm with Eosinophilia Associated with PCM1-JAK2 Rearrangement. | 17 |
| 31598574 | 2019 | Hodgkin Lymphoma and Cutaneous T-Cell Lymphoma Sharing the PCM1-JAK2 Fusion and a Common T-Cell Clone. | 17 |
| 37102606 | 2023 | Myeloid/lymphoid neoplasms associated with eosinophilia and rearrangements of PCM1::JAK2 with erythroblastic sarcoma: a case report and literature review. | 15 |
| 29567772 | 2018 | Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2. | 15 |
| 30687064 | 2018 | Septic Shock Predisposed by an Underlying Chronic Neutrophilic Leukemia with an Atypical Presentation; A Case Report. | 14 |
| 31744552 | 2019 | A tricky and rare cause of pulmonary eosinophilia: myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA. | 11 |
| 29797824 | 2018 | PCM1-JAK2 Fusion in a Patient With Acute Myeloid Leukemia. | 10 |
| 34772467 | 2021 | Nanopore sequencing for the screening of myeloid and lymphoid neoplasms with eosinophilia and rearrangement of PDGFRα, PDGFRβ, FGFR1 or PCM1-JAK2. | 10 |
| 35028141 | 2022 | Sequential allogeneic transplantation and ruxolitinib maintenance for a synchronous PCM1-JAK2 positive myeloid sarcoma and acute B-lymphoblastic leukemia. | 10 |
| 26522767 | 2016 | A t(8;9)(p22;p24)/PCM1-JAK2 translocation in a patient with myeloproliferative neoplasm and myeloid sarcoma: first report in Korea. | 8 |
| 36068374 | 2023 | Updates on eosinophilic disorders. | 0 |
| 37283522 | 2023 | The international consensus classification of eosinophilic disorders and systemic mastocytosis. | 0 |
| 34533850 | 2022 | World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management. | 0 |
| 21091042 | 2011 | PCM1-JAK2-fusion: a potential treatment target in myelodysplastic-myeloproliferative and other hemato-lymphoid neoplasms. | 0 |
| 24913195 | 2014 | Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities? | 0 |
| 32472305 | 2020 | Pemigatinib: First Approval. | 0 |
| 35786767 | 2022 | PCM1::JAK2 fusion associates with an atypical form of mycosis fungoides. | 0 |
| 38842862 | 2024 | PCM1::JAK2 myeloproliferative neoplasm suggested by bone marrow histopathological features. | 0 |
| 28028030 | 2017 | Myeloid neoplasms with eosinophilia. | 0 |
| 32862848 | 2020 | Update on CML-Like Disorders. | 0 |
| 32525541 | 2020 | Contemporary Classification and Diagnostic Evaluation of Hypereosinophilia. | 0 |
| 33990705 | 2021 | Myeloid/lymphoid neoplasms with FLT3 rearrangement. | 0 |
| 34994608 | 2021 | Two Cases of Mycosis Fungoides With PCM1-JAK2 Fusion. | 0 |
| 16564930 | 2006 | Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) translocation. | 0 |
| 33890194 | 2021 | Clinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis. | 0 |
| 32279331 | 2020 | Response to tyrosine kinase inhibitors in myeloid neoplasms associated with PCM1-JAK2, BCR-JAK2 and ETV6-ABL1 fusion genes. | 0 |
| 33367495 | 2021 | Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, or FGFR1 or With PCM1-JAK2. | 0 |
| 30401948 | 2019 | Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study. | 0 |
| 15805263 | 2005 | The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. | 0 |
| 18297515 | 2008 | JAK and MPL mutations in myeloid malignancies. | 0 |
| 16034466 | 2005 | PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. | 0 |
| 33166908 | 2020 | Myeloid/lymphoid neoplasms with eosinophilia and FLT3 rearrangement. | 0 |
| 25260694 | 2015 | Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes. | 0 |
| 33502001 | 2021 | Efficacy of ruxolitinib in B-lymphoblastic leukaemia with the PCM1-JAK2 fusion gene. | 0 |
| 16091753 | 2005 | The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene. | 0 |
| 32853379 | 2020 | Transformation to erythroblastic sarcoma from myeloid neoplasm with PCM1-JAK2. | 0 |
| 31423623 | 2019 | World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management. | 0 |
| 23400675 | 2013 | Hematologic malignancies with PCM1-JAK2 gene fusion share characteristics with myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1. | 0 |
| 29044676 | 2017 | World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management. | 0 |
| 26202607 | 2015 | Efficacy of ruxolitinib in myeloid neoplasms with PCM1-JAK2 fusion gene. | 0 |
| 30806106 | 2019 | Myeloid neoplasm with eosinophilia and PCM1-JAK2 associated with acute promyelocytic leukemia with PML-RARA. | 0 |
| 34547879 | 2021 | [Treatment of PCM1-JAK2-positive myeloproliferative neoplasm with eosinophilia using ruxolitinib: a case report]. | 0 |
| 22899477 | 2012 | Ruxolitinib inhibits transforming JAK2 fusion proteins in vitro and induces complete cytogenetic remission in t(8;9)(p22;p24)/PCM1-JAK2-positive chronic eosinophilic leukemia. | 0 |
| 37562364 | 2023 | Sustained Response to Ruxolitinib of Eosinophilia-Associated Myeloproliferative Neoplasm with Translocation t(8;9)(p21;p24). | 0 |
| 16007127 | 2005 | JAK the trigger. | 0 |
| 23701125 | 2013 | Implication of MAPK1/MAPK3 signalling pathway in t(8;9)(p22;24)/PCM1-JAK2 myelodysplastic/myeloproliferative neoplasms. | 0 |
| 16424865 | 2006 | A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma. | 0 |
| 30132131 | 2019 | Genetic alterations of 9p24 in lymphomas and their impact for cancer (immuno-)therapy. | 0 |
| 39105620 | 2024 | TLE3 Is a Novel Fusion Partner of JAK2 in Myeloid/Lymphoid Neoplasm With Eosinophilia Responding to JAK2 Inhibition. | 0 |
| 32886902 | 2020 | Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology. | 0 |
| 23630205 | 2013 | Efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene. | 0 |
| 34105517 | 2021 | JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology. | 0 |
| 29025582 | 2017 | A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with eosinophilia. | 0 |
| 22288769 | 2012 | Chronic eosinophilic leukemia with erythroblastic proliferation and the rare translocation t(8;9)(p22;p24) with PCM1-JAK2 fusion gene: a distinct clinical, pathological and genetic entity with potential treatment target? | 0 |
| 16769584 | 2006 | A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia. | 0 |
| 30585592 | 2018 | [A revised 4 edition WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, 2017: myeloid neoplasms]. | 0 |
| 32827877 | 2020 | Integrated genomic analysis using chromosomal microarray, fluorescence in situ hybridization and mate pair analyses: Characterization of a cryptic t(9;22)(p24.1;q11.2)/BCR-JAK2 in myeloid/lymphoid neoplasm with eosinophilia. | 0 |
| 18594780 | 2008 | Evolutional change of karyotype with t(8;9)(p22;p24) and HLA-DR immunophenotype in relapsed acute myeloid leukemia. | 0 |
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16424865 | 2006 | A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma. | Adélaïde J et al |
| 16564930 | 2006 | Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) translocation. | Bousquet M et al |
| 16007127 | 2005 | JAK the trigger. | Mahon FX et al |
| 16034466 | 2005 | PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation. | Murati A et al |
| 15805263 | 2005 | The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2. | Reiter A et al |
Summary
Fusion gene
PCM1/JAK2 PCM1 (8p22) JAK2 (9p24.1) M t(8;9)(p22;p24)|PCM1/JAK2 PCM1 (8p22) JAK2 (9p24.1) TIC
Citation
Andreas Reiter ; Christoph Walz
t(8;9)(p22;p24) PCM1/JAK2
Atlas Genet Cytogenet Oncol Haematol. 2006-09-01
Online version: http://atlasgeneticsoncology.org/haematological/1329/t(8;9)(p22;p24)-pcm1-jak2
