t(11;14)(q23;q32) KMT2A/CEP170B

2009-07-01   Jean-Loup Huret 

1.Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France

Clinics and Pathology

Disease

Treatment related leukemia (treatment related acute myeloid leukemia, t-AML)

Epidemiology

The involvement of MLL in 11q23 and KIAA0284 in 14q32 was shown in only 2 cases (Burmeister et al., 2008; De Braekeleer et al., 2009). These 2 cases were treatment related leukemia cases (t-AML for: treatment related acute myeloid leukemia). These t-AML cases occurred in a 45-year-old male patient (a M1 case) and in a 65-year-old female patient, 2 years after an urothelial carcinoma and 5 years after a ductal mammary carcinoma respectively. In 1 other case of t(11;14)(q23;q32), a myelodysplastic syndrome case, the involvement of MLL was excluded, and IGH in 14q32 was rearranged (Yujiri et al., 2009). Finally, in 2 other cases of t(11;14)(q23;q32), no molecular studies were available (Kaneko et al., 1982; Hanson et al., 1993). The two latter cases were a biphenotypic leukemia (BAL) case and an acute lymphoblastic leukemia (ALL) in a 33-year-old male patient.

Prognosis

One of the t-AML cases died 2 months after diagnosis, while the other one was lost to follow-up 5 years after diagnosis of the t-AML. The ALL case died 7 months after diagnosis.

Genes Involved and Proteins

Gene name
KMT2A (myeloid/lymphoid or mixed lineage leukemia)
Location
11q23.3
Dna rna description
36 exons, multiple transcripts 13-15 kb.
Protein description
3969 amino acids; 431 kDa; contains two DNA binding motifs (a AT hook and a CXXC domain), a DNA methyl transferase motif, a bromodomain. MLL is cleaved by taspase 1 into 2 proteins before entering the nucleus, called MLL-N and MLL-C. The FYRN and a FRYC domains of native MLL associate MLL-N and MLL-C in a stable complex; they form a multiprotein complex with transcription factor TFIID. MLL is a transcriptional regulatory factor. MLL can be associated with more than 30 proteins, including the core components of the SWI/SNF chromatin remodeling complex and the transcription complex TFIID. MLL binds promotors of HOX genes through acetylation and methylation of histones. MLL is a major regulator of hematopoesis and embryonic development.
Gene name
Location
3q13.13
Protein description
KIAA0284 presents an amino acids similarity of 30% with CEP170. CEP170 is a forkhead-associated domain protein which associates with centrosomes during interphase and with spindle microtubules during mitosis (Guarguaglini et al., 2005).

Result of the Chromosomal Anomaly

Description

5 MLL - 3 KIAA0284

Transcript

The breakpoint was located in intron 9 of MLL. The breakpoint in KIAA0284 was located in intron 2 in one case, and intron 4 in the other case.

Description

N-term MLL - C-term KIAA0284

Bibliography

Pubmed IDLast YearTitleAuthors
186400632008A MLL-KIAA0284 fusion gene in a patient with secondary acute myeloid leukemia and t(11;14)(q23;q32).Burmeister T et al
192548552009A second case of secondary acute myeloblastic leukemia associated with the MLL-KIAA0284 fusion gene.De Braekeleer E et al
156161862005The forkhead-associated domain protein Cep170 interacts with Polo-like kinase 1 and serves as a marker for mature centrioles.Guarguaglini G et al
76878601993Acute biphenotypic leukaemia: immunophenotypic and cytogenetic analysis.Hanson CA et al
69529601982Correlation of karyotype with clinical features in acute lymphoblastic leukemia.Kaneko Y et al
191005182009A novel t(11;14)(q23;q32) in a case of myelodysplastic syndrome.Yujiri T et al

Summary

Fusion gene

KMT2A/CEP170B KMT2A (11q23.3) CEP170B (14q32.33) TIC

Citation

Jean-Loup Huret

t(11;14)(q23;q32) KMT2A/CEP170B

Atlas Genet Cytogenet Oncol Haematol. 2009-07-01

Online version: http://atlasgeneticsoncology.org/haematological/1539/t(11;14)(q23;q32)

External Links