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t(9;22)(q34;q11) BCR/ABL1 in AML

Written1997-09Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

(Note : for Links provided by Atlas : click)


ICD-Morpho 9861/3 AML with mutated NPM1; AML with mutated CEBPA; Acute myeloid leukaemia, NOS
Atlas_Id 1023
Note Although the same hybrid genes issued from ABL and BCR are the hallmark of the t(9;22) translocation, this translocation may be seen in the following diseases: CML, AML, and ALL, and will therefore be described in the 3 different situations: t(9;22)(q34;q11) in CML, t(9;22)(q34;q11) in ALL, t(9;22)(q34;q11) in AML t(9;22)(q34;q11) in AML is herein described
  t(9;22)(q34;q11) G- banding (left) - Courtesy Jean-Luc Lai and Alain Vanderhaegen (3 top) and Diane H. Norback, Eric B. Johnson, and Sara Morrison-Delap, UW Cytogenetic Services (2 bottom); R-banding (right) top: Editor; 2 others Courtesy Jean-Luc Lai and Alain Vanderhaegen); diagram and breakpoints (Editor).

Clinics and Pathology

Disease AML
Phenotype / cell stem origin mostly M1 or M2 AML
Epidemiology 3% of AML; 1% in childhood AML
Prognosis is very poor


Cytogenetics Morphological the chromosomal anomaly disappear during remission, in contrast with BC-CML cases when treated with conventional therapies

Genes involved and Proteins

Gene NameABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Location 9q34.12
Dna / Rna alternate splicing (1a and 1b) in 5'
Protein giving rise to 2 proteins of 145 kDa; contains SH (SRC homology) domains; N-term SH3 and SH2 - SH1 (tyrosine kinase) - DNA binding motif - actin binding domain C-term; widely expressed; localisation is mainly nuclear; inhibits cell growth
Gene NameBCR (Breakpoint cluster region)
Location 22q11.23
Dna / Rna various splicings
Protein main form: 160 KDa; N-term Serine-Treonine kinase domain, SH2 binding, and C-term domain which functions as a GTPase activating protein for p21rac; widely expressed; cytoplasmic localisation; protein kinase; probable role in signal transduction

Result of the chromosomal anomaly

Hybrid gene
  • the crucial event lies on der(22), id est 5' BCR/3' ABL hybrid gene is pathogenic, while ABL/BCR may or may not be expressed;
  • breakpoint in ABL is variable over a region of 200 kb, often between the two alternative exons 1b and 1a, sometimes 5' of 1b, or 3' of 1a, but always 5' of exon 2; - breakpoint in BCR is either (as in ALL cases): 1- in the same region as in CML, called M-bcr (for major breakpoint cluster region), a cluster of 5.8 kb, between exons 12 and 16, also called b1 to b5 of M-bcr; most breakpoints being either between b2 and b3, or between b3 and b4; transcript is 8.5 kb long; this results in a 210 KDa chimeric protein (P210), with the first 902 or 927 amino acids from BCR; 2- in a 35 kb region between exons 1 and 2, called m-bcr (minor breakpoint cluster region), -> 7 kb mRNA, resulting in a 190 KDa protein (P190), with the 427 N-terminal amino acids from BCR
  • Transcript 7 or 8.5 kb
    Fusion Protein
    Description 190 or 210 kDa (see above); BCR/ABL has a cytoplasmic localization, in contrast with ABL, mostly nuclear; this may have a carcinogenetic role. The hybrid protein has an increased protein kinase activity compared to ABL: 3BP1 (binding protein) binds normal ABL on SH3 domain, which prevents SH1 activation; with BCR/ABL, the first (N-terminal) exon of BCR binds to SH2, hidding SH3 which, as a consequence, cannot be bound to 3BP1; thereof, SH1 is activated
    Oncogenesis 1- proliferation is induced: there is activation by BCR/ABL of Ras signal transduction pathway via it's linkage to son-of-sevenless (SOS), a Ras activator; PI3-K (phosphatidyl inositol 3' kinase) pathway is also activated; MYC as well; 2- BCR/ABL inhibits apoptosis; 3- BCR/ABL provokes cell adhesive abnormalities: impaired adherence to bone marrow stroma cells, which allows unregulated proliferation of leukaemic progenitors

    To be noted

    blast crisis is sometimes at the first onset of CML, and those cases may be undistinguishable from true AML with t(9;22) and P210 BCR/ABL hybrid


    The function of BCR/ABL and related proto-oncogenes.
    Gotoh A, Broxmeyer HE
    Current opinion in hematology. 1997 ; 4 (1) : 3-11.
    PMID 9050373
    Molecular insights into the Philadelphia translocation.
    Heisterkamp N, Groffen J
    Hematologic pathology. 1991 ; 5 (1) : 1-10.
    PMID 2050600
    The molecular pathology of chronic myelogenous leukaemia.
    Kurzrock R, Talpaz M
    British journal of haematology. 1991 ; 79 Suppl 1 : 34-37.
    PMID 1931706


    This paper should be referenced as such :
    Huret, JL
    t(9;22)(q34;q11) in AML
    Atlas Genet Cytogenet Oncol Haematol. 1997;1(1):29-31.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    Other genes implicated (Data extracted from papers in the Atlas) [ 3 ]

    Genes ABL1 BCR GRB2

    Translocations implicated (Data extracted from papers in the Atlas)

     t(9;22)(q34;q11) BCR/ABL1 in AML

    External links

    Mitelman databaset(9;22)(q34;q11) [Case List]    t(9;22)(q34;q11) [Transloc-MCList] BCR/ABL1 [Fusion-MCList]
    arrayMap (UZH-SIB Zurich)Topo ( C42) Morph ( 9861/3) -   [auto + random 100 samples .. if exist ]   [tabulated segments]
    Other databaseABL/BCR translocation (9/22) (Bari)
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed
    All articlesautomatic search in PubMed

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