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

Written2006-09Andreas Reiter, Christoph Walz
Medizinische Universitatsklinik, Fakultat fur Klinische Medizin Mannheim der Universitat Heidelberg, Wiesbadener Str. 7-11, 68305 Mannheim, Germany

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Identity

ICD-Topo C420,C421,C424 BLOOD, BONE MARROW, & HEMATOPOIETIC SYS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9837/3 T lymphoblastic leukaemia/lymphoma
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9989/3 Myelodysplastic syndrome, unclassifiable
Atlas_Id 1329

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Epidemiology 15 published cases (plus 3 unpublished), striking male predominance, only 2 females, median age 45.5 years (range, 12-74).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).
 
  Figure 1. t(8;9)(p22;p24) QFQ-banding - Courtesy Marc Muller
 
  Figure 2. FISH: left: JAK2 breakapart probe on overnight cultured cell. The der(8) is marked by the red 5'JAK2 signal and the der(9) is marked by the green 3'JAK signal; right: JAK2 Breakapart probe on interphase nuclei showing a break beetween the 5' and 3' signals; t(8;9)(p22;p24) Ideogram - Courtesy Marc Muller

Genes involved and Proteins

Gene Name PCM1
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
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.
  

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

A t(8;9) translocation with PCM1-JAK2 fusion in a patient with T-cell lymphoma.
Adélaïde J, Pérot 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
 
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, Adélaïde J, Perot C, Talmant P, Giraudier S, Lodé 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
 

Citation

This paper should be referenced as such :
Walz, C ; Reiter, A
t(8;9)(p22;p24)
Atlas Genet Cytogenet Oncol Haematol. 2007;11(1):36-37.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Anomalies/t0809p22p24ID1329.html


Other genes implicated (Data extracted from papers in the Atlas) [ 1 ]

Genes JAK2

Translocations implicated (Data extracted from papers in the Atlas)

 t(8;9)(p22;p24) PCM1/JAK2

External links

PCM1 (8p22) JAK2 (9p24.1)

PCM1 (8p22) JAK2 (9p24.1)

Mitelman databaset(8;9)(p22;p24) [Case List]    t(8;9)(p22;p24) [Association List] Mitelman database (CGAP - NCBI)
arrayMapTopo ( C42) Morph ( 9811/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9837/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9861/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMapTopo ( C42) Morph ( 9989/3) - arrayMap (UZH-SIB Zurich)  [auto + random 100 samples .. if exist ]   [tabulated segments]
 
Mitelman databasePCM1/JAK2 [MCList]  PCM1 (8p22) JAK2 (9p24.1)
TICdbPCM1/JAK2  PCM1 (8p22) JAK2 (9p24.1)
 
Disease databaset(8;9)(p22;p24) PCM1/JAK2
REVIEW articlesautomatic search in PubMed
Last year articlesautomatic search in PubMed
All articlesautomatic search in PubMed


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