January 2022 – Cytogenetics and Laboratory Genetics and Genomics Case 1

Bone marrow banded chromosome analysis was ordered for a 30-year-old man with a suspected diagnosis of acute myeloid leukemia. Banded analysis (Figure 1) has a result of:  

45,X,-Y,add(7)(p11.2),der(8)t(8;21)(q22;q22),der(21)t(7;21)(p15;q22)[20].FISH for t(8;21)(q22;q22) (RUNX1T1/RUNX1) (Figure 2) has a result of: nuc ish(RUNX1T1,RUNX1)x3(RUNX1T1 con RUNX1x1)[369/500]/(RUNX1T1,RUNX1)x3(RUNX1T1 con RUNX1x2)[23/500]

Figure 1: Banded analysis
Figure 2: FISH with RUNX1T1 (red) and RUNX1 (green) probes. One fusion (yellow) is present.

What is the correct interpretation for this case?  

  • The t(7;21) results in a RUNX1/UPS42 fusion and is consistent with AML.
  • The t(8;21) results in a RUNX1/TRPS1 fusion and is consistent with AML.
  • The t(8;21) results in a RUNX1T1/RUNX1 fusion and is consistent with de novo or therapy-related AML.
  • The t(7;21) disrupted the RUNX1T1/RUNX1 fusion from the t(8;21) and is not consistent with AML.

The correct answer is ...

The t(8;21) results in a RUNX1T1/RUNX1 gene fusion and is consistent with de novo or therapy-related acute myeloid leukemia (AML).

The patient’s karyogram demonstrates the presence of both a derivative chromosome 8 from a 8;21 translocation and a derivative chromosome 21 from a 7;21 translocation, along with additional chromatin of undetermined origin attached to the short arm of chromosome 7 and a missing Y chromosome. The t(8;21)(q22;q22) that was the origin of the derivative chromosome 8 results in the fusion of RUNX1T1 and RUNX1, which is associated with AML. FISH subsequently confirmed the presence of the RUNX1T1/RUNX1 fusion gene.

The atypical component of this case was the t(7;21)(p15;q22). The breakpoints for both translocations are the same on chromosome 21. RUNX1 is located on chromosome 21 and RUNX1T1 is located on chromosome 8. The t(8;21) results in different gene fusions on der(8) and der(21). It is the RUNX1T1/RUNX1 fusion gene on der(8) that creates a new oncogenic transcription factor that promotes leukemic transformation. Therefore, even if the fusion product on der(21) is involved in a t(7;21), the fusion product on der(8) remains intact, which is important for this patient’s diagnosis and prognosis.

FISH shows that in the majority of cells, there is one fusion (likely the gene fusion on der(8)) which suggests that the RUNX1T1/RUNX1 fusion on der(21) may be disrupted by the t(7;21) translocation. Regardless of the t(7;21), the presence of the RUNX1T1/RUNX1 fusion is consistent with AML and has a favorable prognosis. 

Lauren Choate

Lauren Choate, Ph.D.

Resident, Laboratory Genetics and Genomics
Mayo Clinic

Jess F Peterson Square Profile pic

Jess Peterson, M.D.

Consultant, Hematopathology
Mayo Clinic
Associate Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

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This post was developed by our Education and Technical Publications Team.