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

1997-09-01   Jean-Loup Huret , Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology



Phenotype stem cell origin

L1 or L2 ALL; most often with B-cell phenotype, rare T-cell cases; heterogeneity of lineage involvement: may either be a multipotent stem cell, or a lymphoid-committed progenitor.


20% of adult ALL, 2-5% of children ALL


frequent CNS involvement, even at diagnosis; blood data: high WBC (50-150 X 109/l).


CD10+ in most cases, sometimes CD19+ CD10-


BMT is indicated


is very poor, especially in lymphoid-committed progenitor cases; the breakpiont in M-bcr or in m-bcr (see below) does not seem to have impact on prognosis.


Cytogenetics morphological

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

Cytogenetics molecular

is useful to uncover a masked Philadelphiachromosome, where chromosomes 9 and 22 all appear to be normal, but wherecryptic insertion of 3 ABL within a chromosome 22 can be demonstrated

Additional anomalies

found in 50 to 80% of cases: +der(22), -7, del(7q)most often, +8, but not an i(17q), in contrast with CML and AML cases;complex karyotypes, often hyperploid, are frequent


t(9;22;V) and apparent t(V;22) or t(9;V), where V is a variablechromosome, may be found, as in CML

Genes Involved and Proteins

Gene name
ABL1 (v-abl Abelson murine leukemia viral oncogene homolog 1)
Dna rna description
alternate splicing (1a and 1b) in 5
Protein description
giving rise to 2 proteins of 145 kDa; contains SH (SRChomology) domains; N-term SH3 and SH2 - SH1 (tyrosine kinase) - DNA bindingmotif - actin binding domain C-term; widely expressed; localisation ismainly nuclear; inhibits cell growth , 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
Gene name
BCR (Breakpoint cluster region)
Dna rna description
various splicings
Protein description
main form: 160 KDa; N-term Serine-Treonine kinase

Result of the Chromosomal Anomaly


  • the crucial event lies on der(22), id est 5 BCR/3 ABLexon of BCR binds to SH2, hidding SH3 which, as a consequence, cannot bebound to 3BP1; thereof, SH1 is activatedtwo alternative exons 1b and 1a, sometimes 5 of 1b, or 3 of 1a, butalways 5 of exon 2; - breakpoint in BCR is either (as in ALL cases): 1- inthe same region as in CML, called M-bcr (for major breakpoint clusterregion), a cluster of 5.8 kb, between exons 12 and 16, also called b1 to b5of M-bcr; most breakpoints being either between b2 and b3, or between b3and b4; transcript is 8.5 kb long; this results in a 210 KDa chimericprotein (P210), with the first 902 or 927 amino acids from BCR; 2- in a 35kb region between exons 1 and 2, called m-bcr (minor breakpoint clusterregion), -> 7 kb mRNA, resulting in a 190 KDa protein (P190), with the 427N-terminal amino acids from BCR , 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)
  • Transcript

    7 or 8.5 kb


    190 or 210 kDa (see above); BCR/ABL has a cytoplasmic


    1- proliferation is induced: there is activation by BCR/ABL ofRas signal transduction pathway via its linkage to son-of-sevenless (SOS),a Ras activator; PI3-K (phosphatidyl inositol 3 kinase) pathway is alsoactivated; MYC as well; 2- BCR/ABL inhibits apoptosis; 3- BCR/ABL provokescell adhesive abnormalities: impaired adherence to bone marrow stromacells, which allows unregulated proliferation of leukaemic progenitors

    Highly cited references

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    No bibliography items were found for this article.



    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 ALL is herein described.
    Atlas Image
    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).


    Jean-Loup Huret ; Jean-Loup Huret

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

    Atlas Genet Cytogenet Oncol Haematol. 1997-09-01

    Online version: http://atlasgeneticsoncology.org/haematological/1024/t0922allid1024