A Novel t(11;12)(q23–24;q24) in a Case of Minimally-Differentiated Acute Myeloid Leukemia (AML-M0)

Cox, Maria Christina; Scanzani, A.; Poeta, Giovanni Del; Venditti, Adriano; Paterini, Paola; Derme, Valentina; Sgro, Rosanna; Masi, M; Amadori, Sergio

doi:10.1016/s0165-4608(99)00179-x

Cited by 3 publications

(1 citation statement)

References 23 publications

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“…This chromosome 12q24 region is also implicated in AML. [98][99][100] Further down-regulation of SMRT by antisense strategy conferred transformation of fibroblasts in cooperation with overexpressed hTert (telomerase) and SV40-LargeT in soft-agar assays. In addition, reconstitution in lymphoma cell lines with exogenous SMRT expression induced apoptosis.…”

Section: Transcribed Isoforms Of T(8;21) and Their Impact On Leukemogmentioning

confidence: 99%

Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts

Peterson

Boyapati

Ahn

et al. 2007

Blood

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IntroductionAcute myeloid leukemia (AML) is a heterogeneous disease that is classified based on the presence of specific cytogenetic abnormalities as well as the French-American-British (FAB) classification of the leukemic cells and immunophenotype. One of the common translocations identified in leukemia is between chromosome 8q22 and chromosome 21q22 ( Figure 1a). 1 It is associated with nearly 40% of cases of FAB-M2 AML and 8% to 20% of all cases of AML depending on the genetic background and geographic location of the population. The (8;21) translocation is also observed in approximately 6% of AML M1 and, more rarely, in AML M0, M4, M5, and other myeloproliferative syndromes. 2,3 The involved genes are, on chromosome 8, MTG8 or ETO, meaning myeloid translocation gene or eight twenty-one, respectively, 4,5 and AML1 (acute myeloid leukemia factor 1) on chromosome 21. 4 The commonly used name for the t(8;21) fusion protein is AML1-MTG8 or AML1-ETO, and we refer to it as AML1-ETO in this review. AML1 was also discovered from other studies that are not related to t(8;21) and has several different names. 6 Its HUGO (Nomenclature Committee of the Human Genome Organization) name is RUNX1. In correlation, MTG8/ETO is named RUNX1T1 for RUNX1 translocation 1.The t(8;21) generates the 2 fusion genes AML1-ETO and ETO-AML1 ( Figure 1B). AML1-ETO mRNA is easily detectable using polymerase chain reaction (PCR) primers on 2 sides of the fusion point. However, ETO-AML1 mRNA was not identified using a similar approach (E. Kanbe, D.-E.Z., unpublished data, February 2003). This result indicates that the ETO-AML1 transcript is not expressed, is expressed at an extremely low level, or is highly unstable due to degradation. All of the studies on t(8;21) have therefore focused on AML1-ETO.Most of the coding region of the ETO gene is fused to the AML1 amino terminus containing the DNA-binding runt homology domain (RHD) to generate an AML1-ETO fusion protein ( Figure 1C). 4,5,7 The ETO gene has 14 exons. The original cloned AML1-ETO cDNA contained ETO exons 2 through 11; the fusion transcript produces an AML1-ETO protein of 752 amino acids ( Figure 1C). 8 The ETO portion of the full-length AML1-ETO protein contains 3 proline-serine-threonine (PST)-rich regions and 4 Nervy homology regions (NHR1-4) ( Figure 1C). 9 The PST-rich regions have multiple potential kinase phosphorylation sites (SP [Serine-Proline] and TP [Threonine-Proline]). Phosphorylation of ETO has been reported although no kinase involved in its phosphorylation has been identified. 10 NHR1, also called the TAF (TATA box binding protein associated factor) homology domain, shares a sequence similarity with TAF110 and other related TAFs. NHR2 has a hydrophobic amino acid heptad repeat, which is critical for ETO oligomerization. 11 NHR3 contains a predicted coiled-coil structure. NHR4 is a myeloid-Nervy-DEAF1 (MYND) homology domain with 2 predicted zinc finger motifs.Expression of the AML1-ETO fusion gene is under the control of the AML1 promoter. The AML1 gene has 2 promot...

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Section: Transcribed Isoforms Of T(8;21) and Their Impact On Leukemogmentioning

confidence: 99%

Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts

Peterson

Boyapati

Ahn

et al. 2007

Blood

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Acute Myeloid Leukemia

Naeim¹,

Rao²

2008

Hematopathology

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Comparison between conventional banding analysis and FISH screening with an AML-specific set of probes in 260 patients

Cox¹,

Paterini²,

Venditti³

et al. 2003

Hematol J

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Fluorescence in situ hybridization (FISH) is becoming popular in the diagnosis of clonal chromosomal abnormalities. We set up a fast FISH procedure using an extensive set of specific probes. Conventional banding analysis (CBA) and FISH were compared in 260 newly diagnosed acute myeloid leukemia (AML) patients. For FISH the following probes were used: MLL, CBF-beta/MYH11, ETV-6/AML1; AML1/ETO, BCR/ABL, PML/RAR, c-MYC, TP53, RB1, 5q31/5p15.2, 5q33-34, 7q31/CEP7, 20q13; CEP 4, X, Y. Result time was 96 h for CBA versus 5 h for FISH from direct harvest. CBA showed clonal abnormalities in 41% (n=105/260), normal karyotype in 39% (n=102/260) and failed in 20% (n=53/260). FISH screened all patients and detected abnormalities in 39% (n=102/260); CBA and FISH together identified abnormalities in 49% (n=128/260). In six patients with normal CBA and in eight patients with clonal karyotype, it detected further cryptic abnormalities. CBA showed clonal abnormalities in 13% of patients negative at FISH (n=21/158). FISH screening does not add relevant information to CBA, but is the quickest method for detecting major genetic abnormalities in AML. The speed of FISH is very valuable in AML-M3/M3v because PML/RAR+ patients require specific therapy. Furthermore, we suggest FISH screening in failed, complex or suboptimal quality chromosome and specific FISH analysis for 5q, 7q, 12p, 17p, inv(16), t(11q23) in order to implement CBA accuracy.

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A Novel t(11;12)(q23–24;q24) in a Case of Minimally-Differentiated Acute Myeloid Leukemia (AML-M0)

Cited by 3 publications

References 23 publications

Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts

Acute myeloid leukemia with the 8q22;21q22 translocation: secondary mutational events and alternative t(8;21) transcripts

Acute Myeloid Leukemia

Comparison between conventional banding analysis and FISH screening with an AML-specific set of probes in 260 patients

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