Translocation t(1;16)(p31;q24) rearranging CBFA2T3 is specific for acute erythroid leukemia

Micci, Francesca; Thorsen, Jim; Haugom, Lisbeth; Zeller, Bernward; Tierens, Anne; Heim, Sverre

doi:10.1038/leu.2011.100

Cited by 18 publications

(23 citation statements)

References 10 publications

(12 reference statements)

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“…In a previous publication of ours 1 we showed the involvement of the myeloid translocation gene-related protein 2 gene ( CBFA2T3 ) in a case of acute erythroid leukemia with the translocation t(1;16)(p31;q24). Because of lack of material available for analysis, we could not with certainty determine the leukemogenic mechanism, whether it be generation of a fusion gene with CBFA2T3 as one of the partners or loss of tumor suppressor activity, in which case genes KANK1 and L1TD1 , both homozygously lost, might be of the essence.…”

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confidence: 79%

“…The involvement of the NFIA gene fits well with the fluorescence in situ hybridization (FISH) data on chromosome 1 previously obtained and published. 1 The presence of the NFIA/CBFA2T3 fusion was verified by PCR using the NFIA-956 F and CBFA2T3–622 R primer combination (Supplementary Table 2). A specific PCR product of about 500 bp was identified and directly sequenced (Figure 1a).…”

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confidence: 99%

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High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24)

et al. 2012

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confidence: 79%

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High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24)

et al. 2012

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“…Both chromosome bands, 1p36 and 3q21, were seen rearranged in the abnormal karyotype of the present case. Likewise, on chromosome band 16p11, the FUS gene was found to be rearranged and fused to ERG in a subset of AML with t(16;21)(p11;q22) (1,2), and on 16q24, the CBFA2T3 gene was found, also in AML, to be a partner gene in the fusions RUNX1-CBFA2T3 [t(16;21)(q24;q22)], NFIA-CBFA2T3 [t(1;16)(p31;q24)], and CBFA2T3-GLIS2 [inv(16)(p13q24)] (22,23,29,30). The aberrations der(2)t(2;3)(q21;q21) and der(10)t(1;10)(q32;q24) could also conceivably generate fusion genes.…”

Section: Discussionmentioning

confidence: 99%

“…Except the ZC3H7-BCOR , which was detected in a tumor whose karyotype contained two chromosome translocations (19), all the other studies started with malignancies in which the karyotype had a single chromosomal translocation. In hematologic malignancies, likewise, an NFIA-CBFA2T3 ( NFIA is located in 1p31) chimeric transcript was found in an acute erythroid leukemia with the translocation t(1;16)(p31;q24) and a FISH-detected split of CBFA2T3 in 16q24 (22,23). The same approach comparing karyotypic and sequencing data was also used to identify the ZMYND8-RELA fusion in a congenital acute erythroid leukemia carrying a t(11;20)(p11;q13) translocation as a sole chromosome aberration (24).…”

Section: Introductionmentioning

confidence: 97%

Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia

et al. 2013

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Sequential combination of cytogenetics and RNA-sequencing (RNA-Seq) has been shown to be an efficient approach to detect pathogenetically important fusion genes in neoplasms carrying only one or a few chromosomal rearrangements. We performed RNA-Seq on an acute myeloid leukemia in a 2-year-old girl with the karyotype 46,XX,add(1)(p36), der(2)t(2;3)(q21;q21),del(3)(q21),der(10)t(1;10)(q32;q24),der(16)(2qter-->2q21::16p11-->16q24::16p11-->16pter)[13]/46,XX[2] and identified a cryptic FUS/ERG fusion gene. PCR and direct sequencing verified the presence of the FUS-ERG chimeric transcript in which exon 7 of FUS from 16p11 (nt 904 in sequence with accession number NM_004960 version 3) was fused in frame to exon 8 of ERG from sub-band 21q22.2 (nt 967 in NM_004449 version 4). The FUS-ERG transcript found here has been reported in only two other cases of childhood leukemia, in a 1-year-old boy and an 8-month-old boy, both diagnosed with precursor B cell ALL. The fusion transcript codes for a 497 amino acid residues FUS-ERG protein and, similar to other AML-related FUS-ERG fusion proteins, contains both functional domains (TR1 and TR2) of the transactivation domain of FUS and the ETS domain of ERG. The clinical significance, if any, of the amino acid residues which are coded by the exons 8, 9 and 10 of ERG in the fusion FUS-ERG proteins, remains unclear.

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“…A translocation t(1;16)(p31;q24) rearranging the CBFA2T5 gene encoding for z protein in the myeloid translocation gene family of transcriptional corepressors has recently been described as associated with AEL. 16 Erythropoiesis is mediated by a relatively small number of lineage-restricted transcription factors, including GATA-1, SCL/TAL1, LMO2, LDB1, and KLF1. 17 GATA-1 is a Zn-finger DNA binding transcription factor that activates expression of numerous genes in concert with SCL/TAL-1.…”

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confidence: 99%

Acute myeloid leukemia with expanded erythropoiesis

Porwit¹,

Vardiman²

2011

Haematologica

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Depending on previous clinical history, number of blasts in the bone marrow, and results of cytogenetic analysis, hematologic malignancies with expanded erythropoiesis (more than 50% of bone marrow erythropoietic cells) may fall under various categories of the 2008 edition of the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (Table 1). 1The general threshold of blast percentage for the diagnosis of acute myeloid leukemia (AML) is 20% of total peripheral blood or bone marrow cells. However, cases with fewer than 20% blasts and more than 50% of erythroid precursors in the bone marrow are classified as acute erythroid leukemia (AEL, erythroid/myeloid) if blasts account for 20% or more of the non-erythroid cells. If blasts constitute less than 20% of nonerythroid cells, the cases are classified into various categories of myelodysplastic syndromes (MDS). Patients with 80% or more of bone marrow cells representing immature cells committed exclusively to the erythropoietic lineage are classified as having pure erythroid leukemia.The WHO 2008 classification has also defined the category of AML with myelodysplasia-related changes (AML-MRC) as acute leukemia with 20% or more peripheral blood or bone marrow blasts with morphological features of myelodysplasia or a prior history of MDS or MDS/myeloproliferative neoplasm or MDS-related genetic abnormalities (Table 2), and absence of prior cytotoxic therapy and the specific genetic abnormalities that would classify the case as AML with recurrent genetic abnormalities. Several studies confirmed the negative prognostic significance of the MDSrelated genetic abnormalities.2,3 Concerning cases with more than 50% erythroid precursors, the authors of the WHO 2008 classification stated that cases with 20% or more blasts should be classified as AML-MRC if MDS-related cytogenetic abnormalities or multilineage dysplasia in more than 50% of cells in two or more lineages are found. It has also been pointed out that patients with AEL often have complex karyotypes but the possibility of including AEL cases with complex karyotypes and less than 20% bone marrow blasts in the AML-MRC category has not been addressed. 1Several groups have recently discussed the diagnosis, definition and prognosis of AEL and MDS with expanded erythropoiesis (>50% erythropoietic precursors in bone marrow smears).4-6 The common findings were high incidence of unfavorable karyotypes, low frequency of NPM1, FLT3 and RAS mutations, and poor prognosis. 4,[6][7][8][9][10] In this issue of Haematologica, Bacher et al. 4 have compared some genetic and clinical aspects of AML and MDS with expanded erythropoiesis. On the basis of the observed better 2-year overall survival rate of MDS patients (n=104) in comparison to those classified as having AML (combined cohort of 77 AEL and 24 AML-MRC), the authors propose continuing separating MDS with expanded erythropoiesis from AML. It should be noted that the patients in this study classified as having MDS and carrying an unfavorab...

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Translocation t(1;16)(p31;q24) rearranging CBFA2T3 is specific for acute erythroid leukemia

Cited by 18 publications

References 10 publications

High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24)

High-throughput sequencing identifies an NFIA/CBFA2T3 fusion gene in acute erythroid leukemia with t(1;16)(p31;q24)

Cryptic FUS-ERG fusion identified by RNA-sequencing in childhood acute myeloid leukemia

Acute myeloid leukemia with expanded erythropoiesis

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