Acute Promyelocytic Leukemia with a Rare &lt;b&gt;&lt;i&gt;PML&lt;/i&gt;&lt;/b&gt; Exon 4/&lt;b&gt;&lt;i&gt;RARA&lt;/i&gt;&lt;/b&gt; Exon 3 Fusion Transcript Variant

Oh, Se Jin; Park, Tae Sung; Lee, Jin Young; Mun, Yeung Chul; Seong, Chu-Myong; Marschalek, Rolf; Meyer, Claus; Chung, Wha Soon; Huh, Jungwon

doi:10.1159/000348551

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…The clinical and biological impact of these atypical isoforms remains unclear. A few reports demonstrated that PML break points downstream intron 6 are potentially associated with poor prognosis and an aggressive disease course, whereas other studies described cases with atypical PML/RARA with clinical outcome similar to that of patients with typical fusion transcripts …”

Section: Introductionmentioning

confidence: 99%

“…A few reports demonstrated that PML break points downstream intron 6 are potentially associated with poor prognosis and an aggressive disease course, [8][9][10][11] whereas other studies described cases with atypical PML/RARA with clinical outcome similar to that of patients with typical fusion transcripts. 9,[12][13][14][15][16] In this study, we report the characterization of three cases of APL with novel atypical PML/RARA transcripts, which were not clearly detectable using standard molecular procedure.…”

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confidence: 99%

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Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia

Iaccarino

Divona

Ottone

et al. 2018

Genes Chromosomes & Cancer

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Once the diagnostic suspicion of acute promyelocytic leukemia (APL) has been raised, international guidelines recommend prompt initiation of tailored therapy and supportive care, while awaiting for genetic confirmation of the diagnosis, and the identification of the specific PML/RARA isoform by reverse transcriptase polymerase chain reaction (RT‐PCR). Depending on the PML break point, usually located within intron 6, exon 6, or intron 3, different PML/RARA transcript isoforms may be generated, that is, long (bcr1), variant (bcr2), and short (bcr3), respectively. We report here the characterization of three APL cases harboring atypical PML/RARA transcripts, which were not clearly detectable after standard RT‐PCR amplification. In all three cases, clinical, morphological, and immunophenotypic features were consistent with APL. Direct sequencing allowed the identification of atypical break points within the PML and RARA genes. Then, we designed a patient‐specific quantitative real‐time PCR for the atypical transcripts, which allowed for specific quantitative evaluation of minimal residual disease (MRD) during follow‐up. Despite the rarity of APL cases with an atypical PML/RARA fusion, our study indicates that an integrated laboratory approach, employing several diagnostic techniques is crucial to timely diagnose APL. This approach allows prompt initiation of specific targeted treatment and reliable MRD monitoring in atypical APL cases.

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia

Iaccarino

Divona

Ottone

et al. 2018

Genes Chromosomes & Cancer

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Molecular analysis of more than 140 gene fusion variants and aberrant activation of EVI1 and TLX1 in hematological malignancies

et al. 2017

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Gene fusions are observed in abnormal chromosomal rearrangements such as translocations in hematopoietic malignancies, especially leukemia subtypes. Hence, it is critical to obtain correct information about these rearrangements in order to apply proper treatment techniques. To identify abnormal molecular changes in patients with leukemia, we developed a multiplex reverse transcriptase polymerase chain reaction (MRT-PCR) protocol and investigated more than 140 gene fusions resulting from variations of 29 prevalent chromosomal rearrangements along with EVI1 and TLX1 oncogenic expression in the presence of optimized primers. The potential of the MRT-PCR method was approved by evaluating the available cell lines as positive control and confirmed by sequencing. Samples from 53 patients afflicted with hematopoiesis malignancies were analyzed. Results revealed at least one chromosomal rearrangement in 69% of acute myeloid leukemia subjects, 64% of acute lymphoblastic leukemia subjects, and 81% of chronic myeloid leukemia subjects, as well as a subject with hypereosinophilic syndrome. Also, five novel fusion variants were detected. Results of this study also showed that chromosomal rearrangements, both alone and in conjunction with other rearrangements, are involved in leukemogenesis. Moreover, it was found that EVI1 is a suitable hallmark for hematopoietic malignancies.

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Acute Promyelocytic Leukemia with a Rare <b><i>PML</i></b> Exon 4/<b><i>RARA</i></b> Exon 3 Fusion Transcript Variant

Cited by 2 publications

References 13 publications

Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia

Identification and monitoring of atypical PML/RARA fusion transcripts in acute promyelocytic leukemia

Molecular analysis of more than 140 gene fusion variants and aberrant activation of EVI1 and TLX1 in hematological malignancies

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