Atlas of Genetics and Cytogenetics in Oncology and Haematology
t(9;22)(q34;q11) in ALL
| Identity |
| 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, ANLL, 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 ANLL t(9;22)(q34;q11) in ALL is herein described. |
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| 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 | ALL |
| Phenotype / cell stem 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. |
| Epidemiology | 20% of adult ALL, 2-5% of children ALL |
| Clinics | frequent CNS involvement, even at diagnosis; blood data: high WBC (50-150 X 109/l). |
| Cytology | CD10+ in most cases, sometimes CD19+ CD10- |
| Treatment | BMT is indicated |
| Prognosis | 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 |
| 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 Philadelphia' chromosome, where chromosomes 9 and 22 all appear to be normal, but where cryptic 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 ANLL cases; complex karyotypes, often hyperploid, are frequent |
| Variants | t(9;22;V) and apparent t(V;22) or t(9;V), where V is a variable chromosome, may be found, as in CML |
| Genes involved and Proteins |
| Gene Name | ABL |
| Location | 9q34 |
| 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 Name | BCR |
| Location | 22q11 |
| 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 |
| Description | |
| Transcript | 7 or 8.5 kb |
| 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 |
| External links |
| To be noted |
| blast crisis is sometimes at the first onset of CML, and those cases may be undistinguishable from true ALL with t(9;22) and P210 BCR/ABL hybrid. |
| Bibliography |
| Prognostic implications of breakpoint and lineage heterogeneity in Philadelphia-positive acute lymphoblastic leukemia: a review. |
| Secker-Walker LM, Craig JM |
| Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 1993 ; 7 (2) : 147-151. |
| PMID 8426467 |
| 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 |
| Contributor(s) |
| Written | 09-1997 | Jean-Loup Huret |
| Citation |
| This paper should be referenced as such : |
| Huret JL . t(9;22)(q34;q11) in ALL. Atlas Genet Cytogenet Oncol Haematol. Septem
ber 1997 . URL : http://AtlasGeneticsOncology.org/Anomalies/t0922ALL.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Sat Jul 3 11:54:16 CEST 2010 |
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