1,721,009 research outputs found
FUSION CIRCRNAS FROM THE KMT2A:AFF1 CHIMERIC GENE IN PEDIATRIC B-ALL PATIENTS AND CELL LINES HARBORING THE T(4;11)(Q21.3-Q22.1;Q23.3) TRANSLOCATION
No full textIntroduction: Circular RNAs (circRNAs) are endogenous transcripts
originated as back-splicing products. Their circular structure confers
higher stability than linear transcripts, resulting in their involvement,
when deregulated, in several human diseases, including cancer. Increasing literature documents a predominant non-coding role as micro RNA
sponges or transcriptional regulators, affecting the expression of genes
involved in cell proliferation, invasion, apoptosis, and angiogenesis. circRNAs are also generated by the back-splicing of linear fusion transcripts derived from genomic rearrangements, giving rise to fusion circRNAs (f-circRNAs), as demonstrated in hematological and solid tumors
harboring recurrent chromosomal rearrangements.
Methods: By analyzing six bone marrow (BM) samples from pediatric patients at diagnosis of B-cell Acute Lymphoblastic Leukemia (BALL) and two cell lines (SEM and MV4-11), we investigated if the
linear KMT2A:AFF1 fusion transcript, originated by the recurrent balanced t(4;11)(q21.3-q22.1;q23.3) translocation, might generate f-circRNAs. We performed RT-PCR and Sanger sequencing experiments with
divergent primers, designed on each linear fusion transcript sequence,
on RNAse R-digested RNA samples, using a pool of normal BM samples
and the pre-B cell line NALM-6 as negative controls. RT-qPCR also
evaluated the KMT2A:AFF1 f-circRNA expression in positive and negative samples, including B-ALL patients with the t(12;21) translocation
or a normal karyotype.
Results: The RT-PCR and Sanger sequencing results in SEM and
MV4-11 cell lines indicated the generation of three f-circRNAs showing
the back-splicing of AFF1 exon 8 with either KMT2A exon 2 or exon 1
and AFF1 exon 11 with KMT2A exon 2. The obtained products were not
digested by RNAse R treatment, confirming their circular structure.
Notably, the first and the third isoforms were also observed in pediatric
B-ALL patients with the t(4;11) translocation, but not in patients without
this rearrangement, indicating specificity for t(4;11) positive patients.
Furthermore, one patient, tested in samples at onset and relapse, displayed the persistence of both f-circRNAs isoforms.
Conclusions: Identifying specific f-circRNAs from the
KMT2A:AFF1 fusion transcript is of relevance, as this evidence could
help better understand the role of the t(4;11) rearrangement in the biology
of pediatric B-ALL. The oncogenic role of such transcripts is under evaluation by in vitro studies. Furthermore, circRNAs and f-circRNAs are
considered novel “liquid biopsy” biomarkers for early and non-invasive
diagnosis of tumors, as well as therapeutic targets in human cancer.
Therefore, such molecules may be crucial for future diagnostic/followup approaches and personalized thera
A novel translocation t(2;9)(q14;p12) in AML-M2 with an uncommon phenotype: myeloperoxidase-positive and myeloid antigen-negative
No full textMolecular cytogenetic characterization of a novel additional chromosomal aberration in blast crisis of a Ph-positive chronic myeloid leukemia.
No full textMOLECULAR CHARACTERIZATION OF FOUR MYELOID LEUKEMIA CASES WITH A t(15;21) TRANSLOCATION DISRUPTING RUNX1
No full textConcomitant tetrasomy 3q and trisomy 18 in CD5(-), CD13(+) chronic lymphocytic leukemia.
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A novel t(2;10)(q31;p12) balanced translocation in acute myeloid leukemia
No full textWe describe a case of acute myeloid leukemia M5 showing a balanced t(2;10) (q31;p12) translocation. This has never been described before as the sole cytogenetic abnormality in a bone marrow cell clone at onset. Using fluorescence in situ hybridization with properly designed bacterial artificial chromosome probes, we mapped the breakpoint regions on both derivative chromosomes 2 and 10: der(2) and der(10), respectively. The MPP7 gene, disrupted by the breakpoint on chromosome 10, was juxtaposed upstream of both HNRNA3 and NFE2L2 genes on chromosome 2, without the formation of any fusion gene. Using real-time quantitative polymerase chain reaction, we tested the possible disregulation of any of the breakpoint-associated genes as a consequence of the translocation, but we found no statistically significant alteration. Considering the potential role of this clonal cytogenetic abnormality in leukemogenesis, we speculate that this translocation could have an impact on additional genes mapping outside the breakpoint regions. However, the limited amount of RNA material available prevented us from testing this hypothesis in this present case
t(15;17) in acute promyelocytic leukemia is not associated with submicroscopic deletions on der(17)
No full textGenomic deletions on the third chromosome involved in variant t(9;22) chronic myeloid leukaemia cases
No full textA fluorescence in situ hybridization study of complex t(9;22) in two chronic myelocytic leukemia cases with a masked Philadelphia chromosome.
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