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

2018-02-01   Tatiana Gindina 

1.Cytogenetics Lab, Raisa Gorbacheva Memorial Institute of Childrens Oncology, Hematology and Transplantation at First Pavlov St. Petersburg State Medical University, Saint-Petersburg, Russia; tatgindina@gmail.com
2.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


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

Clinics and Pathology


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.


Median patients age was 51 (range 14-84) years. Sex ratio was 2 male : 1 female patients.


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].


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 name
BCR (Breakpoint cluster region)
Protein description
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. , 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.
Gene name
JAK2 (janus kinase 2)
Protein description
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].

Result of the Chromosomal Anomaly


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.
Atlas Image
Nucleotide and amino acid sequence across the BCR/JAK2 fusion breakpoint.

Detection protocole

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: 5tcataccggcacatctccacac-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.


The fusion protein was not detected on Western blots.
Atlas Image
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.


The BCR/JAK2 protein contains the BCR coiled-coil domain fused to the JH1-tyrosine-kinase domain of JAK2.


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]. 


Pubmed IDLast YearTitleAuthors
239048142013Atypical chronic myeloid leukemia with t(9;22)(p24,11.2), a BCR-JAK2 fusion gene.Bellesso M et al
185038282008A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11) in a patient with acute myeloid leukemia.Cirmena G et al
151983542004Utility of routine classical cytogenetic studies in the evaluation of suspected lymphomas: results of 279 consecutive lymph node/extranodal tissue biopsies.Cook JR et al
223842562012Transforming and tumorigenic activity of JAK2 by fusion to BCR: molecular mechanisms of action of a novel BCR-JAK2 tyrosine-kinase.Cuesta-Domínguez Á et al
225491262012BCR-JAK2 fusion as a result of a translocation (9;22)(p24;q11.2) in a patient with CML-like myeloproliferative disease.Elnaggar MM et al
160014312005A BCR-JAK2 fusion gene as the result of a t(9;22)(p24;q11.2) translocation in a patient with a clinically typical chronic myeloid leukemia.Griesinger F et al
220182742011Two alternatively spliced 5'BCR/3'JAK2 fusion transcripts in a myeloproliferative neoplasm with a three-way t(9;18;22)(p23;p11.3;q11.2) translocation.Impera L et al
185379782008Leukaemia cutis in atypical chronic myeloid leukaemia with a t(9;22) (p24;q11.2) leading to BCR-JAK2 fusion.Lane SW et al
252606942015Limited duration of complete remission on ruxolitinib in myeloid neoplasms with PCM1-JAK2 and BCR-JAK2 fusion genes.Schwaab J et al
205945922010Novel JAK2 rearrangement resulting from a t(9;22)(p24;q11.2) in B-acute lymphoblastic leukemia.Tirado CA et al
234326892013A BCR-JAK2 fusion gene from ins(22;9)(q11;p13p24) in a patient with atypical chronic myeloid leukemia.Xu Y et al


Fusion gene

Atlas Image
G-banded chromosomes showing t(9;22)(p24;q11.2)


Tatiana Gindina

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

Atlas Genet Cytogenet Oncol Haematol. 2018-02-01

Online version: http://atlasgeneticsoncology.org/haematological/1331/t(9;22)(p24;q11-2)

Historical Card

2005-11-01 t(9;22)(p24;q11.2) BCR/JAK2 by  Stefan 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

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