HAEM5:B-lymphoblastic leukaemia/lymphoma with BCR::ABL1 fusion

Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes

This page was converted to the new template on 2023-11-30. The original page can be found at HAEM4:B-Lymphoblastic Leukemia/Lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1.

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

Put your text here and fill in the table (Instruction: Can include references in the table)

Signs and Symptoms	EXAMPLE Asymptomatic (incidental finding on complete blood counts) EXAMPLE B-symptoms (weight loss, fever, night sweats) EXAMPLE Fatigue EXAMPLE Lymphadenopathy (uncommon)
Laboratory Findings	EXAMPLE Cytopenias EXAMPLE Lymphocytosis (low level)

editv4:Clinical Features

The content below was from the old template. Please incorporate above.

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

Put your text here

Immunophenotype

Put your text here and/or fill in the table

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)

Put your text here and fill in the table

Chromosomal Rearrangement	Genes in Fusion (5’ or 3’ Segments)	Pathogenic Derivative	Prevalence	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE t(9;22)(q34;q11.2)	EXAMPLE 3'ABL1 / 5'BCR	EXAMPLE der(22)	EXAMPLE 20% (COSMIC) EXAMPLE 30% (add reference)	Yes	No	Yes	EXAMPLE The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).

editv4:Chromosomal Rearrangements (Gene Fusions)

The content below was from the old template. Please incorporate above.

Put your text here and/or fill in the table

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%

editv4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).

Please incorporate this section into the relevant tables found in:

• Chromosomal Rearrangements (Gene Fusions)
• Individual Region Genomic Gain/Loss/LOH
• Characteristic Chromosomal Patterns
• Gene Mutations (SNV/INDEL)

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.

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.)

Chr #	Gain / Loss / Amp / LOH	Minimal Region Genomic Coordinates [Genome Build]	Minimal Region Cytoband	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE 7	EXAMPLE Loss	EXAMPLE chr7:1- 159,335,973 [hg38]	EXAMPLE chr7	Yes	Yes	No	EXAMPLE Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference).  Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
EXAMPLE 8	EXAMPLE Gain	EXAMPLE chr8:1-145,138,636 [hg38]	EXAMPLE chr8	No	No	No	EXAMPLE Common recurrent secondary finding for t(8;21) (add reference).

editv4:Genomic Gain/Loss/LOH

The content below was from the old template. Please incorporate above.

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

Characteristic Chromosomal Patterns

Put your text here (EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis)

Chromosomal Pattern	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE Co-deletion of 1p and 18q	Yes	No	No	EXAMPLE: See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).

editv4:Characteristic Chromosomal Aberrations / Patterns

The content below was from the old template. Please incorporate above.

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).

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.)

Gene; Genetic Alteration	Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)	Prevalence (COSMIC / TCGA / Other)	Concomitant Mutations	Mutually Exclusive Mutations	Diagnostic Significance (Yes, No or Unknown)	Prognostic Significance (Yes, No or Unknown)	Therapeutic Significance (Yes, No or Unknown)	Notes
EXAMPLE: TP53; Variable LOF mutations EXAMPLE: EGFR; Exon 20 mutations EXAMPLE: BRAF; Activating mutations	EXAMPLE: TSG	EXAMPLE: 20% (COSMIC) EXAMPLE: 30% (add Reference)	EXAMPLE: IDH1 R123H	EXAMPLE: EGFR amplification				EXAMPLE:  Excludes hairy cell leukemia (HCL) (add reference).

Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.

Epigenomic Alterations

Put your text here

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

Gene; Genetic Alteration	Pathway	Pathophysiologic Outcome
EXAMPLE: BRAF and MAP2K1; Activating mutations	EXAMPLE: MAPK signaling	EXAMPLE: Increased cell growth and proliferation
EXAMPLE: CDKN2A; Inactivating mutations	EXAMPLE: Cell cycle regulation	EXAMPLE: Unregulated cell division
EXAMPLE:  KMT2C and ARID1A; Inactivating mutations	EXAMPLE:  Histone modification, chromatin remodeling	EXAMPLE:  Abnormal gene expression program

editv4:Genes and Main Pathways Involved

The content below was from the old template. Please incorporate above.

BCR and ABL1

Genetic 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.

Familial Forms

Put your text here (Instructions: Include associated hereditary conditions/syndromes that cause this entity or are caused by this entity.)

Additional Information

Put your text here

Links

ABL1

BCR

Put your links here (use "Link" icon at top of page)

References

(use the "Cite" icon at the top of the page) (Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted. If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference.)

Notes

*Primary authors will typically be those that initially create and complete the content of a page.  If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage).  Additional global feedback or concerns are also welcome. *Citation of this Page: “B-lymphoblastic leukaemia/lymphoma with BCR::ABL1 fusion”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 11/30/2023, https://ccga.io/index.php/HAEM5:B-lymphoblastic_leukaemia/lymphoma_with_BCR::ABL1_fusion.