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t(9;22)(p24;q11.2) BCR/JAK2

Written2005-11Stefan K Bohlander
Department of Medicine III, University Hospital Grosshadern, Marchioninistr. 15, D-81377 Munich, Germany or/ bGSF, Clinical Cooperative Group Leukemia, Marchioninistr. 25, D-81377 Munich, Germany
Updated2018-02Tatiana Gindina
Cytogenetics Lab, Raisa Gorbacheva Memorial Institute of Children's Oncology, Hematology and Transplantation at First Pavlov St. Petersburg State Medical University, Saint-Petersburg, Russia;

Abstract Review on t(9;22)(p24;q11.2) BCR/JAK2, with data on clinics, and the genes involved.

Keywords Chromosome 9; Chromosome 22; t(9;22)(p24;q11.2); BCR; JAK2.

(Note : for Links provided by Atlas : click)


ICD-Topo C420,C421,C424
ICD-Morpho 9876/3 Atypical chronic myeloid leukaemia, BCR-ABL1 negative
ICD-Morpho 9975/3 Chronic myelogenous leukaemia, BCR-ABL1 positive; Myeloproliferative neoplasm, unclassifiable; Myelodysplastic/myeloproliferative neoplasm, unclassifiable
ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
ICD-Morpho 9811/3 B lymphoblastic leukaemia/lymphoma, NOS
ICD-Morpho 9687/3 Burkitt lymphoma
Atlas_Id 1331
  G-banded chromosomes showing t(9;22)(p24;q11.2)

Clinics and Pathology

Disease Atypical chronic myeloid leukemia (CML), Myeloproliferative neoplasm, unclassifiable; Myelodisplastic/myeloproliferative neoplasm, unclassifiable; Acute myeloid leukemia, NOS; B lymphoblastic leukaemia/ lymphoma, NOS; Burkitt lymphoma.
The translocation t(9;22)(p24;q11.2) JAK2/BCR was found in 11 cases. There were seven patients with myeloproliferative disorders [Griesinger et al., 2005; Lane et al., 2008; Impera et al., 2011; Belesso et al., Elnaggar et al., 2012; Xu et al., 2013; Scwaab et al., 2014], one patient with AML [Cirmena et al., 2008]. ALL was diagnosed in 2 patients [Tirado et al., 2010; Cuesta- Dominguez et al., 2012], Burkitt lymphoma in one patient [Cook et al., 2004].
Should be noted, in a case of Burkitt lymphoma that the molecular study was not be performed. In one patient with ALL, the JAK2/BCR fusion has been proved by molecular methods, but in another one this fusion was not not established.
Epidemiology Median patient's age was 51 (range 14-84) years. Sex ratio was 2 male : 1 female patients.
Treatment Some patients with the myeloproliferative disease had a response to hydroxyurea and/or interferon alfa and achieved partial or complete remission [Griesinger et al., 2005; Impera et al., 2011; Xu et al., 2013]. One patient had a good response to ruxolitinib but relapsed after 18 months [Schwaab et al., 2014]. No patients, who achieved remission of the disease after treatment with tyrosine kinase inhibitors [Griesinger et al., 2005; Impera et al., 2011; Belesso et al., 2013]. Allogeneic and autologous hematopoietic stem cell transplantation was performed for four and one patient, respectively [Cirmena et al., 2008; Tirado et al., 2010; Belesso et al., 2013; Scwaab et al., 2014; Cuesta-Dominguez et al., 2012].
Prognosis Until recently, the prognosis and therapeutic options for patients with BCR/JAK2 fusion genes were rather different. The fusion genes are seen in cases with an aggressive clinical course with rapid progression, usually within the first two years after diagnosis [Griesinger et al., 2005; Impera et al., 2011; Belesso et al., 2013]. In some patients, long-term survival frequently has been achieved after autologous or allogeneic SCT [Tirado et al., 2010; Cuesta-Dominguez et al., 2012].


Cytogenetics Molecular FISH with a BCR/ABL1 probe (dual color dual fusion) will show a split of the BCR signal but no fusion signals and two normal ABL1 signals. FISH with a JAK2 probe (break-apart) will display a split of one JAK2 signal (one co-localized green/red signal corresponding to the regular gene copy, and one red signal and one green signal, suggesting a breakpoint within the JAK2 locus).
Additional anomalies Six patients had translocation t(9;22)(p24;q11.2) as a sole aberration [Griesinger et al., 2005; Cirmena et al., 2008; Lane et al., 2008; Tirado et al., 2010; Belesso et al., 2013]. In one patient the additional chromosomal aberrations, such as 7q deletion and trisomy 19 were found at blast crisis [Griesinger et al., 2005]. An insertion ins(22;9)(q11;p13p24) was found in 1 patient [Xu et al., 2013]. A three-way translocation with the participation of chromosomes 9, 22 and 18 was observed in 2 cases [Impera et al., 2011; Schwaab et al, 2014]. In a case of atypical Burkitt lymphoma, the translocation t(9;22)(p24;q11.2) was accompanied by t(8;14)(q24;q32) [Cook et al., 2004].

Genes involved and Proteins

Gene NameBCR (Breakpoint cluster region)
Location 22q11.23
Protein The function of the normal BCR gene product is not clear. The protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac. There are two transcript variants, encoding different isoforms.
Gene NameJAK2 (janus kinase 2)
Location 9p24.1
Protein JAK2 is a non-receptor tyrosine kinase protein that is essential for signaling through a variety of cytokine receptors and is required for normal hematopoiesis. Activation of the JAK2-cytokine receptor complex leads to the recruitment and JAK2-mediated phosphorylation of STAT5 proteins whose subsequent dimerization and nuclear translocation induces target gene transcription [Cuesta-Dominguez et al., 2012].
A recurrent dominant gain-of-function mutation in JAK2, JAK2V617F, results in constitutional activation of its kinase domain and has been widely established to be causally related to myeloproliferative disorders.

Result of the chromosomal anomaly

Hybrid gene
Note The chimeric transcripts display the fusion of the first exon of BCR to exon 19 or exon 17 or exon 15 of JAK2, respectively [Xu et al., 2013; Scwaab et al., 2014; Cuesta-Dominguez et al., 2012; Elnaggar et al., 2012; Impera et al., 2011]. Another variant, with fusion of BCR exon 14 to JAK2 exon 11, has been reported in one patient with acute myeloid leukemia [Cirmena et al., 2008]. Only the BCR/JAK2 fusion transcript was detected. The reciprocal JAK2-BCR fusion transcript could not be amplified.
  Nucleotide and amino acid sequence across the BCR/JAK2 fusion breakpoint.
Detection The fusion transcript can be detected by RT-PCR using the 5' BCR sense primer: 5'-cagaactcgcaacagtccttc-3'(bp 1602-1622) and the 3' JAK2 antisense primer: 5'tcataccggcacatctccacac-3' (bp 3100-3081). A PCR product of 300 bp should be expected. Please note that since only one case is known, the breakpoints may vary slightly in future cases. This might necessitate the design of different primers.
Fusion Protein
Note The fusion protein was not detected on Western blots.
  Note that this is just the hypothetical BCR/JAK2 fusion protein. Numbers are amino acids from start of protein. The fusion protein contains the coiled-coiled domain of BCR and the kinase domain (PK1 or JH1) of JAK2.
Description The BCR/JAK2 protein contains the BCR coiled-coil domain fused to the JH1-tyrosine-kinase domain of JAK2.
Oncogenesis It has been demonstrated by preclinical studies that the kinase domain of JAK2 is activated through oligomerization mediated by the coiled-coil domain of BCR, as occurred in the constitutive activation of BCR/ABL. The BCR/JAK2 induces STAT5 activation and elicits BCRxL gene expression. These factors promote tumorigenic properties and lead to increased cell survival [Cuesta-Dominguez et al., 2012]. 


Atypical chronic myeloid leukemia with t(9;22)(p24,11
Bellesso M, Santucci R, Dias DF, Centrone R, Elias RC
2), a BCR-JAK2 fusion gene Rev Bras Hematol Hemoter
PMID 23904814
A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11) in a patient with acute myeloid leukemia
Cirmena G, Aliano S, Fugazza G, Bruzzone R, Garuti A, Bocciardi R, Bacigalupo A, Ravazzolo R, Ballestrero A, Sessarego M
Cancer Genet Cytogenet 2008 Jun;183(2):105-8
PMID 18503828
Utility of routine classical cytogenetic studies in the evaluation of suspected lymphomas: results of 279 consecutive lymph node/extranodal tissue biopsies
Cook JR, Shekhter-Levin S, Swerdlow SH
Am J Clin Pathol 2004 Jun;121(6):826-35
PMID 15198354
Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of action of a novel BCR-JAK2 tyrosine-kinase
Cuesta-Domínguez , Ortega M, Ormazábal C, Santos-Roncero M, Galán-Díez M, Steegmann JL, Figuera , Arranz E, Vizmanos JL, Bueren JA, Río P, Fernández-Ruiz E
PLoS One 2012;7(2):e32451
PMID 22384256
BCR-JAK2 fusion as a result of a translocation (9;22)(p24;q11
Elnaggar MM, Agersborg S, Sahoo T, Girgin A, Ma W, Rakkhit R, Zorrilla I, Leal A
2) in a patient with CML-like myeloproliferative disease Mol Cytogenet
PMID 22549126
A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11
Griesinger F, Hennig H, Hillmer F, Podleschny M, Steffens R, Pies A, Wörmann B, Haase D, Bohlander SK
2) translocation in a patient with a clinically typical chronic myeloid leukemia Genes Chromosomes Cancer
PMID 16001431
Two alternatively spliced 5'BCR/3'JAK2 fusion transcripts in a myeloproliferative neoplasm with a three-way t(9;18;22)(p23;p11
Impera L, Lonoce A, Fanfulla DA, Moreilhon C, Legros L, Raynaud S, Storlazzi CT
3;q11 2) translocation
PMID 22018274
Leukaemia cutis in atypical chronic myeloid leukaemia with a t(9;22) (p24;q11
Lane SW, Fairbairn DJ, McCarthy C, Nandini A, Perry-Keene J, Kennedy GA
2) leading to BCR-JAK2 fusion Br J Haematol
PMID 18537978
Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes
Schwaab J, Knut M, Haferlach C, Metzgeroth G, Horny HP, Chase A, Tapper W, Score J, Waghorn K, Naumann N, Jawhar M, Fabarius A, Hofmann WK, Cross NC, Reiter A
Ann Hematol 2015 Feb;94(2):233-8
PMID 25260694
Novel JAK2 rearrangement resulting from a t(9;22)(p24;q11
Tirado CA, Chen W, Huang LJ, Laborde C, Hiemenz MC, Valdez F, Ho K, Winick N, Lou Z, Koduru P
2) in B-acute lymphoblastic leukemia Leuk Res
PMID 20594592
A BCR-JAK2 fusion gene from ins(22;9)(q11;p13p24) in a patient with atypical chronic myeloid leukemia
Xu Y, Yin J, Pan J, Wu C, Wang Q, Yao H, Wu D, Chen S, Sun A
Leuk Lymphoma 2013 Oct;54(10):2322-4
PMID 23432689


This paper should be referenced as such :
Gindina T
t(9;22)(p24;q11.2) BCR/JAK2;
Atlas Genet Cytogenet Oncol Haematol. in press
On line version :
History of this paper:
Bohlander, SK. t(9;22)(p24;q11.2). Atlas Genet Cytogenet Oncol Haematol. 2006;10(2):123-124.

Translocations implicated (Data extracted from papers in the Atlas)

 t(9;22)(p24;q11.2) BCR/JAK2

External links

Mitelman databaset(9;22)(p24;q11.2) [Case List]    t(9;22)(p24;q11.2) [Transloc-MCList] BCR/JAK2 [Fusion-MCList]
arrayMap (UZH-SIB Zurich)Morph ( 9876/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9975/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9811/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
arrayMap (UZH-SIB Zurich)Morph ( 9687/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
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indexed on : Mon May 14 13:40:27 CEST 2018

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