A PML/RARA chimeric gene on chromosome 12 in a patient with acute promyelocytic leukemia (M4) associated with a new variant translocation: t(12;15;17)(q24;q24;q11)

Bennour, Ayda; Tabka, Ikram; Youssef, Yosra Ben; Zaier, Monia; Hizem, Sondess; Khélif, Abderrahim; Sarkhosh, Ali; Sennana, Halima

doi:10.1007/s12032-012-0409-3

Cited by 8 publications

(8 citation statements)

References 21 publications

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“…A case of a PML/RARA chimeric gene on chromosome 12 (t(12;15;17)(q24;q24;q11) has also been recently described. 22 Other investigators have found cases morphologically and immunophenotypically diagnostic of APL without RARA rearrangements; however, RARA may still be involved in these instances by a cryptic mutation or epigenetic mechanisms. 3 More studies on both of these types of cases are needed.…”

Section: Cytogenetic and Molecular Featuresmentioning

confidence: 99%

Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations

Adams

Nassiri²

2015

Archives of Pathology &Amp; Laboratory Medicine

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The majority of patients with acute promyelocytic leukemia (APL) manifest the t(15;17)(q24.1;q21.2) translocation; however, a minor but significant proportion of patients with APL harbor complex, cryptic, or variant translocations, which typically involve RARA. With the exception of ZBTB16/RARA, these variants have similar morphologic and immunophenotypic features as classic APL. Study of the variant forms of APL not only gives insight into the pathogenesis of APL but also allows us to understand the mechanism of retinoid therapy. It is important to identify these cryptic and variant translocations because certain variants, including ZBTB16/RARA and STAT5B/RARA, are resistant to treatment with all-trans retinoic acid, arsenic trioxide, and anthracyclines. A cute promyelocytic leukemia (APL), comprising 5% to 8% of cases of acute myeloid leukemia (AML), is one of the best studied and understood hematopoietic malignancies. Unlike other forms of AML, APL is unique in that it can cause coagulopathy and death if not readily diagnosed.1,2 Morphologically classified as AML-M3 by the French-American-British (FAB) classification, APL is typically characterized by neoplastic proliferation of cells in the bone marrow with a promyelocytic phenotype and the balanced reciprocal translocation t(15;17) (q24.1;q21.2), which results in the expression of the promyelocytic leukemia (PML)-retinoic acid receptor-a (RARA) fusion protein.

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Section: Cytogenetic and Molecular Featuresmentioning

confidence: 99%

Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations

Adams

Nassiri²

2015

Archives of Pathology &Amp; Laboratory Medicine

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“…Although none has been found to involve BCR-ABL1, 20 patients with PML-RARA rearrangements have been reported to date. [5][6][7] The chromosomal translocation in our patient could not be detected by conventional cytogenetic analysis or by FISH but only by multiplex RT-PCR. Direct sequencing analysis revealed a small cryptic insertion in ABL1 exon13, resulting in a BCR-ABL1 fusion transcript.…”

Section: Discussionmentioning

confidence: 56%

A Patient with Philadelphia-Negative Acute Lymphoblastic Leukemia with a FISH-Negative Cryptic BCR-ABL1 Rearrangement Detected by PCR and Sequencing Analysis

Lee

Sohn

et al. 2015

HTIJ

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The BCR-ABL1 rearrangement found in hematologic malignancies such as chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). About 5-10% of patients with CML and ALL lack cytogenetic evidence of the Ph chromosome detected only by fluorescence in situ hybridization (FISH) and/or reverse transcription-polymerase chain reaction (RT-PCR) without any cytogenetic evidence of Ph chromosome. Here we describe a patient with Ph-negative ALL and a FISH-negative cryptic BCR-ABL1 rearrangement, as confirmed by RT-PCR and sequencing analyses. A 20-year-old female with Down syndrome and relapsed ALL was referred to our hospital. All 20 metaphase cells analyzed had a karyotype by conventional methods of 47, XX, +21 and FISH analysis yielded a signal for BCR-ABL1 consistent with a normal pattern. However, multiplex RT-PCR revealed an atypical band indicating the possibility of BCR-ABL1 translocation, which was confirmed by Split-out PCR, real-time PCR and direct sequencing. We revealed that this patient has a dual transcription of typical b3a2 and atypical b2a2 resulted from partial duplication of BCR exon 13, combined with ABL1 exon 2. Although cryptic BCR-ABL1 rearrangements are rare, they affect treatment regimens, making them clinically important. Precise molecular work up along with standard diagnostic tools used to detect BCR-ABL1 rearrangements are recommended for these patients.Citation: Lee N, Lee H, Sohn J, et al. A patient with philadelphia-negative acute lymphoblastic leukemia with a FISH-negative cryptic BCR-ABL1 rearrangement detected by PCR and sequencing analysis.

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“…These include t(14;17)(q22;q21), t(8;17)(p21;q21), t(1;17)(p36;q21), and t(7;17)(q36;q22) . Lately a case with t(12;15;17)(q24;q24;q11) resulting in PML‐RARα hybrid gene on chromosome 12 has been reported …”

Section: Cytogenetic Evaluationmentioning

confidence: 99%

“…23 Lately a case with t (12;15;17)(q24;q24;q11) resulting in PML-RARα hybrid gene on chromosome 12 has been reported. 24 Regardless of the disease complexity and rare failure of cytogenetic analysis in detecting t(15;17) in APL patients, still cytogenetic analysis should always be the first line of examinations to be carried out in patients presumed of having APL, since t(15;17) is ubiquitously present in most of these patients. Ideally commercially available relatively small cosmids probes specific for PML-RARα hybrid gene can be used.…”

Section: Cytogenetic Evaluationmentioning

confidence: 99%

Pathogenetic implication of fusion genes in acute promyelocytic leukemia and their diagnostic utility

et al. 2018

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Acute promyelocytic leukemia (APL) has been recognized as a discrete subset of hematopoietic malignancies constituting approximately 10% of acute myeloid leukemia cases. The hallmark reciprocal chromosomal translocation t(15;17) involving fusion between the retinoic acid receptor (RARα) gene and promyelocytic leukemia (PML) gene is a characteristic feature in APL which consequently results in the emergence of PML-RARα chimeric gene. This gene has been substantiated to be responsible for cellular transformation and is a prime target of all-trans-retinoic acid (ATRA) as well as arsenic-trioxide (ATO) therapy. Since this initial discovery, about 10 diverse translocation partner genes of RARα have been reported that result in variant APL forms strongly suggesting that disruption of RARα underlies its pathogenesis. The nature of the fusion partner has a significant bearing upon disease characteristics including sensitivity to retinoids and ATO and thereby underpins the need for rapid and accurate diagnosis and also demands a highly specific treatment approach. In this article we laid emphasis on the rearrangement of the RARα gene and its different fusion partners resulting in variant forms of APL, their implication in underlying molecular pathogenesis of APL and also the different diagnostic modalities that should be employed for their rapid and accurate diagnosis.

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A PML/RARA chimeric gene on chromosome 12 in a patient with acute promyelocytic leukemia (M4) associated with a new variant translocation: t(12;15;17)(q24;q24;q11)

Cited by 8 publications

References 21 publications

Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations

Acute Promyelocytic Leukemia: A Review and Discussion of Variant Translocations

A Patient with Philadelphia-Negative Acute Lymphoblastic Leukemia with a FISH-Negative Cryptic BCR-ABL1 Rearrangement Detected by PCR and Sequencing Analysis

Pathogenetic implication of fusion genes in acute promyelocytic leukemia and their diagnostic utility

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