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. 2023 Feb 3;14(2):396.
doi: 10.3390/genes14020396.

Fusion Gene-Based Classification of Variant Cytogenetic Rearrangements in Acute Myeloid Leukemia

Mary Gudipati  1 , Melody Butler  1 , Rima Koka  1 , Maria R Baer  2 , Yi Ning  1
Affiliations

Fusion Gene-Based Classification of Variant Cytogenetic Rearrangements in Acute Myeloid Leukemia

Mary Gudipati et al. Genes (Basel). .

Abstract

Acute myeloid leukemia (AML) represents a heterogeneous disease entity that is continuously moving to a more genetically defined classification. The classification of AML with recurrent chromosomal translocations, including those involving core binding factor subunits, plays a critical role in diagnosis, prognosis, treatment stratification, and residual disease evaluation. Accurate classification of variant cytogenetic rearrangements in AML contributes to effective clinical management. We report here the identification of four variant t(8;V;21) translocations in newly diagnosed AML patients. Two patients showed a t(8;14) and a t(8;10) variation, respectively, with a morphologically normal-appearing chromosome 21 in each initial karyotype. Subsequent fluorescence in situ hybridization (FISH) on metaphase cells revealed cryptic three-way translocations t(8;14;21) and t(8;10;21). Each resulted in RUNX1::RUNX1T1 fusion. The other two patients showed karyotypically visible three-way translocations t(8;16;21) and t(8;20;21), respectively. Each resulted in RUNX1::RUNX1T1 fusion. Our findings demonstrate the importance of recognizing variant forms of t(8;21) translocations and emphasize the value of applying RUNX1::RUNX1T1 FISH for the detection of cryptic and complex rearrangements when abnormalities involving chromosome band 8q22 are observed in patients with AML.

Keywords: RUNX1::RUNX1T1 fusion; acute myeloid leukemia; complex rearrangement; cryptic translocation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cytogenetic findings of Patient 1. (a) A representative karyogram: 45,X,-Y,t(8;14;21)(q22;q32;q22). The derivative 21q was cryptic. (b) FISH using a dual-fusion probe RUNX1(red)/RUNX1T1(green) revealed RUNX1::RUNX1T1 fusion on the derivative 8q.
Figure 2
Figure 2
Cytogenetic findings of Patient 2. (a) A representative karyogram: 45,XY,t(8;10;21)(q22;q25;q22). The derivative 21q was cryptic. (b) FISH using a dual-fusion probe RUNX1(red)/RUNX1T1(green) revealed RUNX1::RUNX1T1 fusion on the derivative 8q.
Figure 3
Figure 3
A representative karyogram of Patient 3: 46,XX,t(8;16;21)(q22;q12-13;q22).
Figure 4
Figure 4
A representative karyogram of Patient 4: 46,X,-Y,t(8;20;21)(q22;q13.2;q22).
See this image and copyright information in PMC

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