t(9;22)(q34;q11) BCR/ABL1 in treatment related leukemia

2003-10-01   Jean-Loup Huret  

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

Clinics and Pathology

Disease

Treatment related acute myeloid leukaemias (t-AML) and lymphocytic leukemias (t-ALL)

Note

The study included 10 cases; t-AML and t-ALL accounted for half cases each. Treatment related acute lymphocytic leukemias (t-ALL) are extremely rare, found in only 20 of 511 cases (4%) in this workshop: 5 cases of t(9;22), 12 cases of t(4;11)(q22;q23), 2 cases of t(8;14)(q24;q32), and 1 case of t(11;19)(q23;p13.3)

Epidemiology

t(9;22)(q34;q11) was found in 2% of treatment related acute leukaemias; sex ratio: 2M/8F

Clinics

Age at diagnosis of the primary disease 45 yrs (range 3-76); age at diagnosis of the t-MDS/t-AML: 64 yrs (range 12-78). Median interval was long: 110 mths (range: 25-310). Primary disease was a solid tumor in 70% of cases (in particular breast cancer) and a hematologic malignancy in 20%; treatment was radiotherapy in 1/10, chemotherapy (6/10), or both (3/10). Treatment included topoisomerase II inhibitors in 4 of 9 cases and alkylating agents in 5/9.

Prognosis

Median survival was very poor: 5 mths, with 14% of patients surviving at 1 yr, and none at 2 yrs.

Result of the Chromosomal Anomaly

Description

5 BCR -3¹ ABL

Highly cited references

Pubmed IDYearTitleCitations
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188271852009Molecular biology of bcr-abl1-positive chronic myeloid leukemia.137
358843632022Mechanisms of Resistance and Implications for Treatment Strategies in Chronic Myeloid Leukaemia.123
288041222018SHP2 is required for BCR-ABL1-induced hematologic neoplasia.99
373371052023Transcriptomic classes of BCR-ABL1 lymphoblastic leukemia.91
385509482023Targeting BCR-ABL1-positive leukaemias: a review article.88
386532452024Integrated drug profiling and CRISPR screening identify BCR::ABL1-independent vulnerabilities in chronic myeloid leukemia.83
376291882023Diagnosis- and Prognosis-Related Gene Alterations in BCR::ABL1-Negative Myeloproliferative Neoplasms.80
390989222024BCR::ABL1 Proteolysis-targeting chimeras (PROTACs): The new frontier in the treatment of Ph(+) leukemias?75
384574942024ERG and c-MYC regulate a critical gene network in BCR::ABL1-driven B cell acute lymphoblastic leukemia.73
383972212024Frequencies of BCR::ABL1 Transcripts in Patients with Chronic Myeloid Leukemia: A Meta-Analysis.67
373732662023Molecular BCR::ABL1 Quantification and ABL1 Mutation Detection as Essential Tools for the Clinical Management of Chronic Myeloid Leukemia Patients: Results from a Brazilian Single-Center Study.66
273663122016New Developments in Chronic Myeloid Leukemia: Implications for Therapy.65
331941572020NPM1 Mutated, BCR-ABL1 Positive Myeloid Neoplasms: Review of the Literature.64
290229012017BCR-ABL1-induced downregulation of WASP in chronic myeloid leukemia involves epigenetic modification and contributes to malignancy.63
342763652021Impact of the Breakpoint Region on the Leukemogenic Potential and the TKI Responsiveness of Atypical BCR-ABL1 Transcripts.62
373860792023MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia.61
382826772023Co-occurrence of JAK2-V617 F mutation and BCR::ABL1 translocation in chronic myeloproliferative neoplasms: a potentially confounding genetic combination.60
332831682020Digital PCR for BCR-ABL1 Quantification in CML: Current Applications in Clinical Practice.58
371610702023Mast cell deficiency prevents BCR::ABL1 induced splenomegaly and cytokine elevation in a CML mouse model.58
321546682020Next-generation sequencing for BCR-ABL1 kinase domain mutations in adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia: A position paper.53
339490402021RAG enhances BCR-ABL1-positive leukemic cell growth through its endonuclease activity in vitro and in vivo.53
355514632022BCR::ABL1 tyrosine kinase inhibitors hamper the therapeutic efficacy of blinatumomab in vitro.51
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396524552025BCR::ABL1-induced mitochondrial morphological alterations as a potential clinical biomarker in chronic myeloid leukemia.51
312892062020Human BCR/ABL1 induces chronic myeloid leukemia-like disease in zebrafish.49
262911292015MAPK15 mediates BCR-ABL1-induced autophagy and regulates oncogene-dependent cell proliferation and tumor formation.47
261790662015BCR/ABL1 and BCR are under the transcriptional control of the MYC oncogene.46
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313118092019Targeting BCR-ABL1 in Chronic Myeloid Leukemia by PROTAC-Mediated Targeted Protein Degradation.42
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349022052022RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia.42
358163602022Inflammation accelerates BCR-ABL1+ B-ALL development through upregulation of AID.41
374008422023BCR::ABL1-like acute lymphoblastic leukaemia: a single institution experience on identification of potentially therapeutic targetable cases.41
315434642019Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants.40
371650012023Targeting Poly(ADP)ribose polymerase in BCR/ABL1-positive cells.40
378079802023High BCR::ABL1 Expression Defines CD34+ Cells with Significant Alterations in Signal Transduction, Short-Proliferative Potential and Self-Renewal Ability.39
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314569472019BCR-ABL1 Doubling-Times and Halving-Times May Predict CML Response to Tyrosine Kinase Inhibitors.37
383958952024Pharmacovigilance study of BCR-ABL1 tyrosine kinase inhibitors: a safety analysis of the FDA adverse event reporting system.36
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285338182017A novel BCR-ABL1 fusion gene with genetic heterogeneity indicates a good prognosis in a chronic myeloid leukemia case.33
360869542023Targeting the PTP1B-Bcr-Abl1 interaction for the degradation of T315I mutant Bcr-Abl1 in chronic myeloid leukemia.32
347716342021Droplet Digital PCR for BCR-ABL1 Monitoring in Diagnostic Routine: Ready to Start?31
299767452018BCR-ABL1 genomic DNA PCR response kinetics during first-line imatinib treatment of chronic myeloid leukemia.28
381539132024Developmental trajectories and cooperating genomic events define molecular subtypes of BCR::ABL1-positive ALL.23
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361955702023Hypoxia-inducible factor 1α inhibitor induces cell death via suppression of BCR-ABL1 and Met expression in BCR-ABL1 tyrosine kinase inhibitor sensitive and resistant chronic myeloid leukemia cells.22
374960242023FISH-negative BCR::ABL1-positive e19a2 chronic myeloid leukaemia: the most cryptic of insertions.21
321279502020BCR-ABL1 transcript decline ratio combined BCR-ABL1(IS) as a precise predictor for imatinib response and outcome in the patients with chronic myeloid leukemia.21
338145002021BCR/ABL1-positive B-lymphoblastic Lymphoma Successfully Treated with Dasatinib-combined Chemotherapy.20
389069622024Asciminib antagonizes transplantable BCR::ABL1-positive lymphoid blast crisis in vivo by targeting malignant stem cells.20
301259552018Consensus on BCR-ABL1 reporting in chronic myeloid leukaemia in the UK.19
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258803912015Clonal distribution of BCR-ABL1 mutations and splice isoforms by single-molecule long-read RNA sequencing.17
316443232020BCR-ABL1-like B-Acute Lymphoblastic Leukemia/Lymphoma: A Comprehensive Review.0
350210692022Development of asciminib, a novel allosteric inhibitor of BCR-ABL1.0
330963222020The specificity of asciminib, a potential treatment for chronic myeloid leukemia, as a myristate-pocket binding ABL inhibitor and analysis of its interactions with mutant forms of BCR-ABL1 kinase.0
386434922024BCR::ABL1 kinase N-lobe mutants confer moderate to high degrees of resistance to asciminib.0
371839662023Ultrasensitive NGS MRD assessment in Ph+ ALL: Prognostic impact and correlation with RT-PCR for BCR::ABL1.0
383947742024Beyond BCR::ABL1-The Role of Genomic Analyses in the Management of CML.0
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330389882020CML - Not only BCR-ABL1 matters.0
348186442022BCR/ABL1-Like Acute Lymphoblastic Leukemia: From Diagnostic Approaches to Molecularly Targeted Therapy.0
296966942018Laboratory testing in BCR-ABL1-like (Philadelphia-like) B-lymphoblastic leukemia/lymphoma.0
282220162017A review of the challenge in measuring and standardizing BCR-ABL1.0
310699762019BCR-ABL1-like B-lymphoblastic leukemia/lymphoma: Review of the entity and detection methodologies.0
305617552019BCR/ABL1-like acute lymphoblastic leukemia: How to diagnose and treat?0
279048892017Reactive oxygen species in BCR-ABL1-expressing cells - relevance to chronic myeloid leukemia.0
356093362022The Dawn of Allosteric BCR-ABL1 Drugs: From a Phenotypic Screening Hit to an Approved Drug.0
316963822019The Hidden Pathogenesis of CML: Is BCR-ABL1 the First Event?0
262972642015Mutations in the BCR-ABL1 Kinase Domain and Elsewhere in Chronic Myeloid Leukemia.0
244073762014Genetic events other than BCR-ABL1.0
241318882014Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia.0
190021922008BCR-ABL1-positive CML and BCR-ABL1-negative chronic myeloproliferative disorders: some common and contrasting features.0
274120402017Measurement of BCR-ABL1 transcripts on the International Scale in the United States: current status and best practices.0
387347862024TIF1β activates leukemic transcriptional program in HSCs and promotes BCR::ABL1-induced myeloid leukemia.0
351717272022MUC4 expression by immunohistochemistry is a specific marker for BCR-ABL1+ and BCR-ABL1-like B-lymphoblastic leukemia.0
271316222016Early BCR-ABL1 Reduction Is Predictive of Better Event-free Survival in Patients With Newly Diagnosed Chronic Myeloid Leukemia Treated With Any Tyrosine Kinase Inhibitor.0
374799512023Mitochondrial Dysfunction in Cardiotoxicity Induced by BCR-ABL1 Tyrosine Kinase Inhibitors -Underlying Mechanisms, Detection, Potential Therapies.0
280357332017Frequency of rare BCR-ABL1 fusion transcripts in chronic myeloid leukemia patients.0
341853932021BCR-ABL1 p210 screening for chronic myeloid leukemia in patients with peripheral blood cytoses.0
373023522023Genetic alterations in the BCR-ABL1 fusion gene related to imatinib resistance in chronic myeloid leukemia.0
370788962023Management of chronic myeloid leukaemia: current treatment options, challenges, and future strategies.0
392170002025SOHO State of the Art Updates and Next Questions | Approach to BCR::ABL1-Like Acute Lymphoblastic Leukemia.0
283310562017Monitoring of childhood ALL using BCR-ABL1 genomic breakpoints identifies a subgroup with CML-like biology.0
345066222022Sequential Development of JAK2V617F Mutation and BCR-ABL1 Fusion in Individual Patients With Myeloproliferative Neoplasms.0
392919322024Low-Level BCR::ABL1 Transcript at Diagnosis in Childhood Leukemia: A 10-Year Single Institution Study.0
243678932014Sensitivity of SNX2-ABL1 toward tyrosine kinase inhibitors distinct from that of BCR-ABL1.0
393746392025New practice of BCR::ABL1 standardization system based on p210 and p190 BCR::ABL1 reference materials.0
258140772015Natural course and biology of CML.0
391678242024Comparative analysis of BCR::ABL1 p210 mRNA transcript quantification and ratio to ABL1 control gene converted to the International Scale by chip digital PCR and droplet digital PCR for monitoring patients with chronic myeloid leukemia.0
317075402020Low prevalence of the BCR-ABL1 fusion gene in a normal population in southern Sarawak.0
397434102024A Review of Clonal Relationships in Myeloproliferative Neoplasms With Co-Mutations of JAK2, CALR or MPL and BCR::ABL1.0
378719002024IGJ and SPATS2L immunohistochemistry sensitively and specifically identify BCR::ABL1+ and BCR::ABL1-like B-acute lymphoblastic leukaemia.0
328715882021Early BCR-ABL1 kinetics are predictive of subsequent achievement of treatment-free remission in chronic myeloid leukemia.0
352964472022The Clinical Significance of BCR-ABL1 Mutations in Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia Who Underwent Allogeneic Hematopoietic Cell Transplantation.0
284375522017BCR-ABL1 transcript types showed distinct laboratory characteristics in patients with chronic myeloid leukemia.0
221187442011Chronic myeloid leukemia: current perspectives.0

Article Bibliography

Pubmed IDLast YearTitleAuthors
119212742002Rare recurring balanced chromosome abnormalities in therapy-related myelodysplastic syndromes and acute leukemia: report from an international workshop.Block AW et al

Summary

Fusion gene

BCR/ABL1 BCR (22q11.23) ABL1 (9q34.12) COF 1739 1740 1741 1742 1743 1744 1745 1746 1747 1748 1751 1752 1753 1754 1755 1756 1757 1758 1759 1760 1761 1762 1763 1764 1765 1766 1768 1769 1771 1773 1774 1775 1777 1778 1779 1780 1781 1782 1783 1788 1789 1791 1793 1794|BCR/ABL1 BCR (22q11.23) ABL1 (9q34.12) FC FUSC001404|BCR/ABL1 BCR (22q11.23) ABL1 (9q34.12) M +der(22)t(9;22)(q34;q11) der(9)del(9)(q34q34)t(9;22)(q34;q11) der(9)ins(9;9)(q?;q34)t(9;22)(q34;q11) der(9)t(9;22)(q34;q11) ins(22;9)(q11;q34q21) ins(22;9)(q11;q34q34) ins(9;22)(q34;q11q11) t(10;9;22)(q25;q34;q11) t(11;9;22)(q12;q34;q11) t(1;9;22)(p34;q34;q11) t(1;9;22)(p35;q34;q11) t(1;9;22)(p36;q34;q11) t(1;9;22)(q21;q34;q11) t(1;9;22)(q24;q34;q11) t(1;9;22)(q32;q34;q11) t(1;9;22)(q42;q34;q11) t(2;9;22)(p13;q34;q11) t(2;9;22)(p21;q34;q11) t(2;9;22)(q11;q34;q11) t(2;9;22)(q37;q34;q11) t(3;22)(p24;q11) t(3;9;22)(p11;q34;q11) t(3;9;22)(p14;q34;q11) t(3;9;22)(p21;q34;q11) t(3;9;22)(p22;q34;q11) t(3;9;22)(p24;q34;q11) t(3;9;22)(p25;q34;q11) t(3;9;22)(q12;q34;q11) t(3;9;22)(q21;q34;q11) t(3;9;22)(q25;q34;q11) t(3;9;22)(q26;q34;q11) t(3;9;22)(q27;q34;q11) t(4;9;22)(p11;q34;q11) t(4;9;22)(p14;q34;q11) t(4;9;22)(p16;q34;q11) t(4;9;22)(q12;q34;q11) t(4;9;22)(q13;q34;q11) t(4;9;22)(q21;q34;q11) t(4;9;22)(q25;q34;q11) t(4;9;22)(q27;q34;q11) t(4;9;22)(q31;q34;q11) t(4;9;22)(q34;q34;q11) t(5;9;22)(p13;q34;q11) t(5;9;22)(p15;q34;q11) t(5;9;22)(q13;q34;q11) t(5;9;22)(q23;q34;q11) t(5;9;22)(q31;q34;q11) t(6;9;22)(p11;q34;q11) t(6;9;22)(p21;q34;q11) t(6;9;22)(p22;q34;q11) t(6;9;22)(p23;q34;q11) t(6;9;22)(p24;q34;q11) t(6;9;22)(p25;q34;q11) t(6;9;22)(q12;q34;q11) t(6;9;22)(q21;q34;q11) t(6;9;22)(q22;q34;q11) t(7;9;22)(p12;q34;q11) t(7;9;22)(p22;q34;q11) t(7;9;22)(q11;q34;q11) t(7;9;22)(q12;q34;q11) t(7;9;22)(q22;q34;q11) t(7;9;22)(q32;q34;q11) t(7;9;22)(q35;q34;q11) t(8;22)(q24;q11) t(8;9;22)(p11;q34;q11) t(8;9;22)(p12;q34;q11) t(8;9;22)(p23;q34;q11) t(8;9;22)(q21;q34;q11) t(8;9;22)(q22;q34;q11) t(9;10;22)(q34;q24;q11) t(9;11;22)(q34;p15;q11) t(9;11;22)(q34;q12;q11) t(9;11;22)(q34;q13;q11) t(9;12;22)(q34;p11;q11) t(9;12;22)(q34;p13;q11) t(9;12;22)(q34;q13;q11) t(9;12;22)(q34;q15;q11) t(9;13;22)(q34;q13;q11) t(9;13;22)(q34;q14;q11) t(9;13;22)(q34;q31;q11) t(9;14;22)(q34;q11;q11) t(9;14;22)(q34;q32;q11) t(9;15;22)(q34;q24;q11) t(9;17;22)(q34;q11;q11) t(9;17;22)(q34;q22;q11) t(9;17;22)(q34;q23;q11) t(9;19;22)(q34;q13;q11) t(9;21;22)(q34;q22;q11) t(9;22)(q34;q11) t(9;22)(q34;q11)t(9;9)(q13;q34)t(9;22) t(9;22;10)(q34;q11;p12) t(9;22;10)(q34;q11;p14) t(9;22;10)(q34;q11;q11) t(9;22;10)(q34;q11;q21) t(9;22;10)(q34;q11;q22) t(9;22;11)(q34;q11;p14) t(9;22;11)(q34;q11;q11) t(9;22;11)(q34;q11;q12) t(9;22;11)(q34;q11;q13) t(9;22;12)(q34;q11;p12) t(9;22;12)(q34;q11;p13) t(9;22;12)(q34;q11;q11) t(9;22;12)(q34;q11;q13) t(9;22;12)(q34;q11;q14) t(9;22;12)(q34;q11;q15) t(9;22;12)(q34;q11;q24) t(9;22;13)(q34;q11;p12) t(9;22;13)(q34;q11;q12) t(9;22;13)(q34;q11;q13) t(9;22;13)(q34;q11;q14) t(9;22;13)(q34;q11;q21) t(9;22;14)(q34;q11;p11) t(9;22;14)(q34;q11;q13) t(9;22;14)(q34;q11;q22) t(9;22;14)(q34;q11;q23) t(9;22;14)(q34;q11;q24) t(9;22;14)(q34;q11;q32) t(9;22;15)(q34;q11;q11) t(9;22;15)(q34;q11;q14) t(9;22;15)(q34;q11;q15) t(9;22;15)(q34;q11;q21) t(9;22;15)(q34;q11;q22) t(9;22;15)(q34;q11;q24) t(9;22;15)(q34;q11;q25) t(9;22;15)(q34;q11;q26) t(9;22;16)(q34;q11;p12) t(9;22;16)(q34;q11;p13) t(9;22;16)(q34;q11;q13) t(9;22;16)(q34;q11;q24) t(9;22;17)(q34;q11;p11) t(9;22;17)(q34;q11;p13) t(9;22;17)(q34;q11;q21) t(9;22;17)(q34;q11;q22) t(9;22;17)(q34;q11;q23) t(9;22;17)(q34;q11;q24) t(9;22;17)(q34;q11;q25) t(9;22;18)(q34;q11;p11) t(9;22;19)(q34;q11;p13) t(9;22;19)(q34;q11;q12) t(9;22;19)(q34;q11;q13) t(9;22;20)(q34;q11;p13) t(9;22;20)(q34;q11;q11) t(9;22;20)(q34;q11;q13) t(9;22;21)(q34;q11;p11) t(9;22;21)(q34;q11;q11) t(9;22;21)(q34;q11;q22) t(9;22;22)(q34;q11;q11) t(9;22;22)(q34;q11;q13) t(9;7;22)(q34;p21;q11) t(9;9;22)(p13;q34;q11) t(9;9;22)(p13;q34;q22) t(9;9;22)(q22;q34;q11) t(9;9;22)(q34;q34;q11) t(X;9;22)(p11;q34;q11) t(X;9;22)(p22;q34;q11) t(X;9;22)(q11;q34;q11) t(X;9;22)(q24;q34;q11) t(Y;9;22)(q12;q34;q11)|BCR/ABL1 BCR (22q11.23) ABL1 (9q34.12) TIC

Note

This data is extracted from a very large study from an International Workshop on treatment related leukemias - restricted to balanced chromosome aberrations (i.e.: -5/del(5q)and -7/del(7q) not taken into account per see), published in Genes,Chromosomes and Cancer in 2002.
Atlas Image
t(9;22)(q34;q11) BCR/ABL1 Partial karyotypes with t(9;22)(q34;q11). Fluorescence in situ hybridization with the Vysis LSI BCR/ABL1 dual color dual fusion probes (Abbott Molecular, US) showing 2 copies of genes on normal (A) and fusion red-green signals on der(9) and der(22) chromosomes, the most frequently encountered FISH pattern in patients with t(9;22)(q34;q11) (B). In a smaller subset of patients a supernumerary Ph may be observed, as an extra der(22) chromosome (C) or it is resent in hyperdiploid karyotypes (D). Atypical fusion patterns include the presence of cryptic fusion signal (E), 1 fusion signal on der(22) chromosome (F), that may be with loss of residual proximal 9q (G). Sporadic variations may include the presence of derivative 9 and 22 chromosomes that result from the formation of isodicentric (H) or isochromosomes with or without 9q deletion (I,J) u2013 Courtesy Adriana Zamecnikova.

Citation

Jean-Loup Huret

t(9;22)(q34;q11) BCR/ABL1 in treatment related leukemia

Atlas Genet Cytogenet Oncol Haematol. 2003-10-01

Online version: http://atlasgeneticsoncology.org/haematological/1300/t(9;22)(q34;q11)-bcr-abl1-in-treatment-related-leukemia