t(8;9)(p22;p24)

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t(8;9)(p22;p24)

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Epidemiology 15 published cases (plus 3 unpublished), striking male predominance, only 2 females, median age 45.5 years (range, 12-74).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

Cytogenetics Morphological t(8;9)(p22;p24).

Probes First probe: 5´ and 3´ regions of PCM1 (RP11-49F3 and RP11-3K23). Second probe: 5´ and 3´ regions of JAK2 (RP11-3H3 and RP11-28A9).

Genes involved and Proteins

Gene Name PCM1 (pericentriolar material 1).

Location 8p22-p21.3.

Dna / Rna 41 exons; alternate splicing.

Protein 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.

Dna / Rna 23 exons.

Protein JAK2 is a tyrosine-protein kinase with transmembrane and tyrosine kinase domains.

Result of the chromosomal anomaly

Hybrid gene
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.

Fusion Protein

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.

External links

Other database t(8;9)(p22;p24) Mitelman database (CGAP - NCBI)

Other database t(8;9)(p22;p24) CancerChromosomes (NCBI)

Other database	t(8;9)(p22;p24)	Mitelman database (CGAP - NCBI)
Other database	t(8;9)(p22;p24)	CancerChromosomes (NCBI)

To be noted

Additional cases are needed to delineate the epidemiology of this rare entity:
you are welcome to submit a paper to our new Case Report section.

Bibliography

The t(8;9)(p22;p24) translocation in atypical chronic myeloid leukaemia yields a new PCM1-JAK2 fusion gene.

Bousquet M, Quelen C, De Mas V, Duchayne E, Roquefeuil B, Delsol G, Laurent G, Dastugue N, Brousset P

Oncogene. 2005 ; 24 (48) : 7248-7252.

PMID 16091753

JAK the trigger.

Mahon FX

Oncogene. 2005 ; 24 (48) : 7125-7126.

PMID 16007127

PCM1-JAK2 fusion in myeloproliferative disorders and acute erythroid leukemia with t(8;9) translocation.

Murati A, Gelsi-Boyer V, Adˆ©laˆØde J, Perot C, Talmant P, Giraudier S, Lodˆ© L, Letessier A, Delaval B, Brunel V, Imbert M, Garand R, Xerri L, Birnbaum D, Mozziconacci MJ, Chaffanet M

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2005 ; 19 (9) : 1692-1696.

PMID 16034466

The t(8;9)(p22;p24) is a recurrent abnormality in chronic and acute leukemia that fuses PCM1 to JAK2.

Reiter A, Walz C, Watmore A, Schoch C, Blau I, Schlegelberger B, Berger U, Telford N, Aruliah S, Yin JA, Vanstraelen D, Barker HF, Taylor PC, O'Driscoll A, Benedetti F, Rudolph C, Kolb HJ, Hochhaus A, Hehlmann R, Chase A, Cross NC

Cancer research. 2005 ; 65 (7) : 2662-2667.

PMID 15805263

A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma.

Adˆ©laˆØde J, Pˆ©rot C, Gelsi-Boyer V, Pautas C, Murati A, Copie-Bergman C, Imbert M, Chaffanet M, Birnbaum D, Mozziconacci MJ

Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2006 ; 20 (3) : 536-537.

PMID 16424865

Myeloproliferative disorders carrying the t(8;9) (PCM1-JAK2) translocation.

Bousquet M, Brousset P

Human pathology. 2006 ; 37 (4) : 500-502.

PMID 16564930

Contributor(s)

Written 09-2006 Andreas Reiter, Christoph Walz

Medizinische Universitatsklinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany

Citation

This paper should be referenced as such :
Reiter A, Walz C . t(8;9)(p22;p24). Atlas Genet Cytogenet Oncol Haematol. September 2006 .
URL : http://AtlasGeneticsOncology.org/Anomalies/t0809p22p24ID1329.html

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Mon May 12 18:12:37 2008

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For comments and suggestions or contributions, please contact us

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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 / cell stem 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 Morphological	t(8;9)(p22;p24).
Probes	First probe: 5´ and 3´ regions of PCM1 (RP11-49F3 and RP11-3K23). Second probe: 5´ and 3´ regions of JAK2 (RP11-3H3 and RP11-28A9).

Gene Name	PCM1 (pericentriolar material 1).
Location	8p22-p21.3.
Dna / Rna	41 exons; alternate splicing.
Protein	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.
Dna / Rna	23 exons.
Protein	JAK2 is a tyrosine-protein kinase with transmembrane and tyrosine kinase domains.

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.

Written	09-2006	Andreas Reiter, Christoph Walz
		Medizinische Universitatsklinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany