t(8;9)(p22;p24) PCM1/JAK2

2006-09-01   Andreas Reiter , Christoph Walz 

1.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15 published cases (plus 3 unpublished), striking male predominance, only 2 females, median age 45.5 years (range, 12-74).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

Atlas Image
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.
Atlas Image
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 IDYearTitleCitations
354722442022PCM1-JAK2 Fusion Tyrosine Kinase Gene-Related Neoplasia: A Systematic Review of the Clinical Literature.0
350281412022Sequential allogeneic transplantation and ruxolitinib maintenance for a synchronous PCM1-JAK2 positive myeloid sarcoma and acute B-lymphoblastic leukemia.0
345338502022World Health Organization-defined eosinophilic disorders: 2022 update on diagnosis, risk stratification, and management.3
349946082021Two Cases of Mycosis Fungoides With PCM1-JAK2 Fusion.1
347724672021Nanopore sequencing for the screening of myeloid and lymphoid neoplasms with eosinophilia and rearrangement of PDGFRα, PDGFRβ, FGFR1 or PCM1-JAK2.0
339907052021Myeloid/lymphoid neoplasms with FLT3 rearrangement.0
347079962021Diagnosis and Treatment of Myeloproliferative Neoplasms With PCM1-JAK2 Rearrangement: Case Report and Literature Review.0
345478792021[Treatment of PCM1-JAK2-positive myeloproliferative neoplasm with eosinophilia using ruxolitinib: a case report].0
342987412021Synoptic Diagnostics of Myeloproliferative Neoplasms: Morphology and Molecular Genetics.0
341055172021JAK2 Rearrangements Are a Recurrent Alteration in CD30+ Systemic T-Cell Lymphomas With Anaplastic Morphology.3
338901942021Clinical and Molecular Approach to Adult-Onset, Neoplastic Monocytosis.0
342058342021T-Cell Lymphoblastic Lymphoma Arising in the Setting of Myeloid/Lymphoid Neoplasms with Eosinophilia: LMO2 Immunohistochemistry as a Potentially Useful Diagnostic Marker.0
335020012021Efficacy of ruxolitinib in B-lymphoblastic leukaemia with the PCM1-JAK2 fusion gene.2
333674952021Myeloid/Lymphoid Neoplasms Associated With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, or FGFR1 or With PCM1-JAK2.5
331669082020Myeloid/lymphoid neoplasms with eosinophilia and FLT3 rearrangement.2
328628482020Update on CML-Like Disorders.1
328278772020Integrated 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.2
325255412020Contemporary Classification and Diagnostic Evaluation of Hypereosinophilia.4
328869022020Myeloid/Lymphoid Neoplasms with Eosinophilia and TK Fusion Genes, Version 3.2021, NCCN Clinical Practice Guidelines in Oncology.4
328533792020Transformation to erythroblastic sarcoma from myeloid neoplasm with PCM1-JAK2.0
324723052020Pemigatinib: First Approval.35
322793312020Response to tyrosine kinase inhibitors in myeloid neoplasms associated with PCM1-JAK2, BCR-JAK2 and ETV6-ABL1 fusion genes.4
322384022020The diagnostic challenges and clinical course of a myeloid/lymphoid neoplasm with eosinophilia and ZBTB20-JAK2 gene fusion presenting as B-lymphoblastic leukemia.1
317445522019A tricky and rare cause of pulmonary eosinophilia: myeloid/lymphoid neoplasm with eosinophilia and rearrangement of PDGFRA.9
308061062019Myeloid neoplasm with eosinophilia and PCM1-JAK2 associated with acute promyelocytic leukemia with PML-RARA.1
314236232019World Health Organization-defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management.33
304019482019Hematopoietic neoplasms with 9p24/JAK2 rearrangement: a multicenter study.11
301321312019Genetic alterations of 9p24 in lymphomas and their impact for cancer (immuno-)therapy.1
306870642018Septic Shock Predisposed by an Underlying Chronic Neutrophilic Leukemia with an Atypical Presentation; A Case Report.2
315985742019Hodgkin Lymphoma and Cutaneous T-Cell Lymphoma Sharing the PCM1-JAK2 Fusion and a Common T-Cell Clone.2
295677722018Molecular genetic characterization of myeloid/lymphoid neoplasms associated with eosinophilia and rearrangement of PDGFRA, PDGFRB, FGFR1 or PCM1-JAK2.14
297978242018PCM1-JAK2 Fusion in a Patient With Acute Myeloid Leukemia.4
305855922018[A revised 4 edition WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues, 2017: myeloid neoplasms].2
290446762017World Health Organization-defined eosinophilic disorders: 2017 update on diagnosis, risk stratification, and management.59
290256012017A neoplasm with FIP1L1-PDGFRA fusion presenting as pediatric T-cell lymphoblastic leukemia/lymphoma without eosinophilia.2
290255822017A novel TRIP11-FLT3 fusion in a patient with a myeloid/lymphoid neoplasm with eosinophilia.1
280280302017Myeloid neoplasms with eosinophilia.56
265227672016A t(8;9)(p22;p24)/PCM1-JAK2 translocation in a patient with myeloproliferative neoplasm and myeloid sarcoma: first report in Korea.3
262026072015Efficacy of ruxolitinib in myeloid neoplasms with PCM1-JAK2 fusion gene.12
252606942015Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes.22
249131952014Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities?14
237011252013Implication of MAPK1/MAPK3 signalling pathway in t(8;9)(p22;24)/PCM1-JAK2 myelodysplastic/myeloproliferative neoplasms.3
236302052013Efficacy of ruxolitinib in chronic eosinophilic leukemia associated with a PCM1-JAK2 fusion gene.12
234006752013Hematologic malignancies with PCM1-JAK2 gene fusion share characteristics with myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, and FGFR1.13
233726692013t(8;9)(p22;p24)/PCM1-JAK2 activates SOCS2 and SOCS3 via STAT5.16
222887692012Chronic 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?2
228994772012Ruxolitinib inhibits transforming JAK2 fusion proteins in vitro and induces complete cytogenetic remission in t(8;9)(p22;p24)/PCM1-JAK2-positive chronic eosinophilic leukemia.18
210910422011PCM1-JAK2-fusion: a potential treatment target in myelodysplastic-myeloproliferative and other hemato-lymphoid neoplasms.5
185947802008Evolutional change of karyotype with t(8;9)(p22;p24) and HLA-DR immunophenotype in relapsed acute myeloid leukemia.1
182975152008JAK and MPL mutations in myeloid malignancies.27
167695842006A combination of cytomorphology, cytogenetic analysis, fluorescence in situ hybridization and reverse transcriptase polymerase chain reaction for establishing clonality in cases of persisting hypereosinophilia.3
165649302006Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) translocation.2
164248652006A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma.17
160917532005The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene.22
160071272005JAK the trigger.1
160344662005PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation.20
158052632005The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.62

Bibliography

Pubmed IDLast YearTitleAuthors
164248652006A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma.Adélaïde J et al
165649302006Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) translocation.Bousquet M et al
160071272005JAK the trigger.Mahon FX et al
160344662005PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation.Murati A et al
158052632005The 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

External Links