Elsevier

Cancer Genetics

Volume 208, Issue 4, April 2015, Pages 148-151
Cancer Genetics

Brief communication
A new variant of KMT2A(MLL)-FLNA fusion transcript in acute myeloid leukemia with ins(X;11)(q28;q23q23)

https://doi.org/10.1016/j.cancergen.2015.03.001Get rights and content

The KMT2A gene (previously known as MLL) located at 11q23 is often involved in recurrent chromosomal translocations that lead to the development of acute leukemia, particularly in infants. Acute leukemias with KMT2A rearrangements have different prognoses, which depend on the partner gene involved in the translocation. The detection of all possible types of KMT2A gene rearrangements is of key importance for the identification of biological subgroups, which may differ in clinical outcome. In this report, we describe a case study of a 7-month-old boy who presented with AML-M4; however, no obvious 11q23 rearrangement was detected in the analyzed karyotype. Fluorescence in situ hybridization evaluation showed a nonstandard signal distribution in blast cells, corresponding to the presence of two KMT2A copies and one additional copy of 5′-KMT2A inserted into the long arm of the X chromosome (ins(X;11)(q28;q23q23)). Subsequent molecular analysis showed a novel variant form of the previously described KMT2A-FLNA fusion gene, in which the KMT2A intron 9 is fused to the FLNA exon 16.

Section snippets

Case report

The patient is a 7-month-old male child who was referred to the Central Clinical Hospital (Tula, Russian Federation) in September 2011 because of pain in his left knee and coxa. Physical examination revealed hepatosplenomegaly and prominent lymphadenopathy. The leukocyte count was 80.7 × 109 cells/L. Morphological, cytochemical, and immunological studies revealed acute myelomonocytic leukemia. The infant was treated according to the Moscow-Minsk-AML-2006 protocol. He received induction therapy

Results

G-banding of the patient sample showed a karyotype 47,XY,+6[14]. The mFISH analysis also didn't reveal any structural aberrations. FISH analysis showed nonstandard disruption of the KMT2A gene on 70 of 100 interphase nuclei. The distribution of signals corresponded to two KMT2A copies and one copy of 5′-KMT2A. FISH analysis on metaphases showed that the additional 5′-KMT2A material localized in the long arm of the X chromosome (Figure 1).

LDI-PCR analysis identified the KMT2A-FLNA fusion gene

Discussion

Until now, only one case of a KMT2A-FLNA fusion gene had been described (8). This was an infant AML case (5-month-old boy with AML M4) that corresponds to our data. Similarly, the fusion gene appeared as a consequence of the insertion of a large portion of chromosome 11 material into the X chromosome. The same mechanism was observed in our case, although the insertion was cryptic. A possible explanation for this phenomenon is that the transcriptional orientation of KMT2A and FLNA is different,

Acknowledgment

The authors thank Aleksey Barinov (Moscow City Cancer Hospital No. 62, Moscow, Russia) for technical assistance.

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