Acute Lymphoblastic Leukemia FISH Panels

Last Literature Review: July 2020 Last Update:
  • Recommended FISH panel for adults with newly diagnosed B-ALL
  • Probes include BCR-ABL1 t(9;22), KMT2A (MLL) 11q23 rearrangement (partner not determined), TCF3 (E2A) rearrangement (partner not determined), IGH rearrangement (partner not determined), MYC rearrangement
  • Recommended FISH panel for children with newly diagnosed B-ALL
  • Probes include BCR-ABL1 t(9;22), KMT2A (MLL) 11q23 rearrangement (partner not determined), ETV6-RUNX1, t(12;21), CEP4, CEP10
  • Diagnosis, prognosis, and monitoring of BCR-ABL1-like B-ALL
  • Probes include CRLF2 rearrangement, JAK2 rearrangement, EPOR rearrangement, CSF1R rearrangement, ABL1 rearrangement, ABL2 rearrangement, PDGFRB rearrangement
  • Order when other major prognostic markers (eg, BCR-ABL1, ETV6-RUNX1) are negative
Testing Strategy

At diagnosis, the minimum ALL workup includes bone marrow aspirate for morphology, immunophenotyping, cytogenetics (eg, karyotyping and fluorescence in situ hybridization [FISH]), and other molecular testing, as indicated.

Acute lymphoblastic leukemia (ALL) is an aggressive leukemia of B- or T-lineage immature lymphoid cells. B-cell ALL (B-ALL) is primarily a disease of early childhood. Fluorescence in situ hybridization (FISH) testing identifies rearrangements in specific genes used in risk stratification and treatment decisions for children and adults newly diagnosed with B-ALL.

Disease Overview

Incidence

B-ALL occurs in 1.6/100,000 individuals per year, and is the most common leukemia in childhood. 

Symptoms

Bone marrow failure (eg, anemia, thrombocytopenia, leukopenia) and constitutional symptoms (eg, fever, lethargy, weight loss) are common.  In children, joint or extremity pain may be the only presenting symptom.  

Genetics

Pediatric ALL Adult ALL Ph-Like ALL

BCR-ABL1

KMT2A (MLL)

ETV6-RUNX1

CEP4

CEP10

BCR-ABL1

KMT2A (MLL)

TCF3 (E2A)

IGH

MYC

CRLF2

JAK2

EPOR

CSF1R

ABL1

ABL2

PDGFRB

Ph, Philadelphia chromosome

Test Interpretation

Test Results

Pediatric FISH

  • Normal: no evidence of BCR-ABL1 t(9;22), KMT2A (MLL) rearrangement, ETV6-RUNX1 t(12;21), RUNX1 amplification or copy number gain with CEP4 and/or CEP10
  • Abnormal: one of the above rearrangements or translocations detected

Adult FISH

  • Normal: no evidence of BCR-ABL1 t(9;22), KMT2A (MLL) rearrangement, TCF3 (E2A) rearrangement, IGH rearrangement, or MYC rearrangement
  • Abnormal: one of the above rearrangements/translocations or copy number change detected

Ph-Like ALL FISH

  • Normal: no evidence of rearrangement involving CRLF2, JAK2, EPOR, CSF1R, ABL1, ABL2, or PDGFRB
  • Abnormal: one of the described rearrangements detected

Prognostic Issues

More information on the prognostic significance of identified genetic rearrangements can be found in the ARUP Consult Acute Lymphoblastic Leukemia topic.

Limitations

Panels detect only the specific aberrations targeted by the FISH probes included. Chromosome alterations outside the regions complementary to these probes will not be detected.

References

Related Information
Acute Lymphoblastic Leukemia - ALL
BCR-ABL1 (BCR::ABL1) Qualitative and Quantitative Testing
Cytogenomic Microarray, Oncology
Leukemia/Lymphoma Phenotyping Evaluation by Flow Cytometry
TPMT and NUDT15