B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1

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Primary Author(s)

Afia Hasnain, MBBS, PhD; Yassmine Akkari, PhD, FACMG

Cancer Category/Type

B-Lymphoblastic Leukemia/Lymphoma

Cancer Sub-Classification / Subtype

B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1

Definition / Description of Disease

B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2) is a neoplasm of lymphoblasts committed to the B-cell lineage in which the blasts harbor a translocation between BCR at 22q11.2 and ABL1 oncogene at 9q34.1. The t(9;22) results in the production of a BCR-ABL1 fusion, also known as the Philadelphia chromosome (Ph+).  

Synonyms / Terminology

  • Philadelphia chromosome
  • Ph+

Epidemiology / Prevalence

  • most common genomic alteration in adult B-ALL (25–30%)
  • detected in only 2–4% of pediatric cases

Clinical Features

The presenting features are generally similar to those seen in patients with other B-ALLs. Most children with B-ALL with BCR-ABL1 are considered to have high risk on the basis of age and white blood cell count (WBC). Patients tend to have a high WBC count at presentation, and although they may have organ involvement, lymphomatous presentations are rare.

Sites of Involvement

Bone marrow

Morphologic Features

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Finding Marker
Positive (universal) CD10, CD19 and TdT
Positive (subset) CD13, CD33 and CD25 (in adults)
Negative (universal) KIT (CD117)
Negative (subset) EXAMPLE CD4

Chromosomal Rearrangements (Gene Fusions)

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Chromosomal Rearrangement Genes in Fusion (5’ or 3’ Segments) Pathogenic Derivative Prevalence
t(9;22)(q34.1;q11.2) 3'ABL1 / 5'BCR der(22)t(9;22) 25-30% in adults

2-4 % in pediatric cases

EXAMPLE t(8;21)(q22;q22) EXAMPLE 5'RUNX1 / 3'RUNXT1 EXAMPLE der(8) EXAMPLE 5%

Characteristic Chromosomal Aberrations / Patterns

The t(9;22) results in the production of a BCR-ABL1 fusion protein. The majority of pediatric and half of adult t(9;22) positive B-ALL involve the minor breakpoint cluster region (m-bcr) encoding a smaller p190 fusion protein in contrast to chronic myelogenous leukemia (CML), where it involves the major breakpoint cluster region (M-bcr). [1]

Genomic Gain/Loss/LOH

The most common accompanying chromosomal abnormalities include monosomy 7 (including deletion of the IKZF1 gene) (18%), monosomy 9 or 9p deletion (9%), and gain of 1q (8%).

Chromosome Number Gain/Loss/Amp/LOH Region
7 Loss chr7:1-159,345,973
9 Loss chr9:1-138,394,717

Gene Mutations (SNV/INDEL)

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Gene Mutation Oncogene/Tumor Suppressor/Other Presumed Mechanism (LOF/GOF/Other; Driver/Passenger) Prevalence (COSMIC/TCGA/Other)

Other Mutations

Type Gene/Region/Other
Concomitant Mutations EXAMPLE IDH1 R123H
Secondary Mutations EXAMPLE Trisomy 7
Mutually Exclusive EXAMPLE EGFR Amplification

Epigenomics (Methylation)

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Genes and Main Pathways Involved

BCR and ABL1

Diagnostic Testing Methods

  • Clinical testing for the BCR-ABL1 fusion includes conventional chromosome studies, dual color, dual fusion FISH analysis and RT- PCR.
  • FISH results can be available within 24 h and should be considered as the first line test.
  • Quantitative RT-PCR can detect specific transcripts at a higher sensitivity, and important at follow up to determine disease status and degree of response.
  • Conventional cytogenetics can also detect variant translocations, additional Philadelphia chromosome resulting in gain of 9q and 22q as well as trisomy 8, and a hyperdiploid karyotype.
  • CMA cannot detect balanced rearrangements such as t(9;22) but it can detect additional copy number abnormalities.
  • An average of 7.8 lesions per case were observed by using CMA in adults with Ph + B-ALL.[2]

Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)

The pediatric and adult Ph + B-ALL has been associated with the worst prognosis of the major cytogenetic subtypes of B- ALL. However, therapy with tyrosine kinase inhibitors (TKIs) has had a significantly favorable effect on outcome. A major molecular response is defined as a ≥3-log reduction in BCR-ABL1 transcript compared with the standardized baseline.

The presence of IKZF1 deletion has been associated with poor outcome and high risk of re- lapse. [3]

Familial Forms

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Other Information

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  1. Woo, Jennifer S.; et al. (2014). "Childhood B-acute lymphoblastic leukemia: a genetic update". Experimental Hematology & Oncology. 3: 16. doi:10.1186/2162-3619-3-16. ISSN 2162-3619. PMC 4063430. PMID 24949228.
  2. Fedullo, Anna Lucia; et al. (02 2019). "Prognostic implications of additional genomic lesions in adult Philadelphia chromosome-positive acute lymphoblastic leukemia". Haematologica. 104 (2): 312–318. doi:10.3324/haematol.2018.196055. ISSN 1592-8721. PMC 6355475. PMID 30190342. Check date values in: |date= (help)
  3. van der Veer, Arian; et al. (2014-03-13). "IKZF1 status as a prognostic feature in BCR-ABL1-positive childhood ALL". Blood. 123 (11): 1691–1698. doi:10.1182/blood-2013-06-509794. ISSN 1528-0020. PMID 24366361.


  1. Arber DA, et al., (2008). Acute myeloid leukaemia with recurrent genetic abnormalities, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, Editors. IARC Press: Lyon, France, p117-118.


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