MicroRNAs as the Target of Deletions on der(9) in Chronic Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2926-2926
Author(s):  
Francesco Albano ◽  
Luisa Anelli ◽  
Antonella Zagaria ◽  
Alessandra Pannunzio ◽  
Antonella Russo Rossi ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Myeloid Leukemia ◽  
Cpg Island ◽  
Chromosome 9 ◽  
Genomic Sequences ◽  
Derivative Chromosome ◽  
The Third ◽  
Genomic Regions ◽  
Third Derivative

Abstract Deletions on der(9) are associated with chronic myeloid leukemia(CML) in 15–18% of cases. To date, the biological significance of this genomic loss in the pathogenesis of CML is unknown. The most plausible hypothesis is that the loss of a tumor suppressor gene may confer a proliferative advantage to the Philadelphia-positive clone. On the other hand, it has now become evident that microRNAs (miRNAs) play an important regulatory role in some hematological malignancies. To investigate the presence of miRNAs within the genomic regions lost on der(9) we analyzed 60 CML patients with der(9) deletions. Methods. Genomic characterization of the deleted sequences was performed by fluorescence in situ hybridization (FISH) using a contig of DNA clones; the miRBase (http://microrna.sanger.ac.uk/) was queried to assess the presence of miRNAs in the der(9) deleted genomic regions. FISH experiments showed that the genomic loss on der(9) of the 9 (centromeric to ABL) and 22 (telomeric to BCR) chromosome sequences ranged from 260 Kb to 54 Mb and from 230 Kb to 12.9 Mb, respectively. Consultation of the miRBase revealed that in 16 (27%) patients there was loss of miRNAs mapping on chromosome 9 whereas no known miRNAs were mapped on the deleted genomic sequences belonging to chromosome 22. Moreover, 4 cases with a complex t(9;22) rearrangement and der(9) deletions showed loss of the miRNAs sequence also on the third derivative chromosome (4p16, 7p14, 13q14, and 11q13, respectively); among them, only in one case the loss of miRNAs on the third derivative was not associated with the miRNAs deletion mapped on chromosome 9. The most recurrent miRNAs deleted on der(9) were mir-219–2 (deleted in 100% of cases) and mir-199-b (lost in 67% of cases). It is noteworthy that mir-219–2 neighbors and overlaps CpG-islands, suggesting a potential role of this miRNA in CpG-island methylation. Experimental studies indicate that miRNAs can function as tumor suppressor genes or as oncogenes. In fact, in chronic lymphocytic leukemia associated with del(13)(q14) it has been demonstrated that the miRNAs loss can induce downregulation of the antiapoptotic BCL-2 protein. The novel evidence that deletions on der(9) in CML are associated with miRNAs loss may shed new light on the significance of genomic sequences loss. Further studies are needed since it is known that some microRNAs may have as many as a few thousand targets, so prediction algorithms and strategies allowing large-scale screening of multiple target genes are required.

Derivative Chromosome 9 Deletions in Chronic Myeloid Leukemia are Associated with Loss of Tumor Suppressor Genes

2004 ◽  
Vol 45 (4) ◽  
pp. 689-694 ◽  
Author(s):  
Giorgina Specchia ◽  
Francesco Albano ◽  
Luisa Anelli ◽  
Clelia Tiziana Storlazzi ◽  
Antonella Zagaria ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Tumor Suppressor ◽  
Tumor Suppressor Genes ◽  
Myeloid Leukemia ◽  
Chromosome 9 ◽  
Derivative Chromosome ◽  
Suppressor Genes

Molecular cytogenetic study of derivative chromosome 9 deletion in chronic myeloid leukemia patients

2011 ◽  
Vol 29 (2) ◽  
pp. 1151-1160 ◽  
Author(s):  
Ayda Bennour ◽  
Ines Ouahchi ◽  
Yosra Ben Youssef ◽  
Monia Zaier ◽  
Mohamed Adnéne Laatiri ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cytogenetic Study ◽  
Chromosome 9 ◽  
Derivative Chromosome ◽  
Molecular Cytogenetic

Derivative chromosome 9 deletions in chronic myeloid leukemia: poor prognosis is not associated with loss of ABL-BCRexpression, elevated BCR-ABL levels, or karyotypic instability

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4547-4553 ◽  
Author(s):  
Brian J. P. Huntly ◽  
Anthony J. Bench ◽  
Eric Delabesse ◽  
Alistair G. Reid ◽  
Juan Li ◽  
...  
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Disease Progression ◽  
Myeloid Leukemia ◽  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Prognostic Indicator ◽  
Genetic Alterations ◽  
Chromosome 9 ◽  
Derivative Chromosome ◽  
The Poor

Deletions of the derivative chromosome 9 have recently been reported in chronic myeloid leukemia. These deletions are large, occur at the time of the Philadelphia (Ph) translocation, span the translocation breakpoint, and represent a powerful prognostic indicator. However, the molecular mechanisms responsible for the poor prognosis associated with deletions are obscure, and several possible models are investigated here. First, we demonstrate that all derivative chromosome 9 deletions detected by fluorescence in situ hybridization were associated with an absence ofABL-BCR expression. However, loss ofABL-BCR expression also occurred without an overt deletion, suggesting the existence of other mechanisms by whichABL-BCR transcription can be abolished. Furthermore, analysis of survival in 160 patients demonstrated that loss ofABL-BCR expression, in contrast to deletion status, was not an indicator of poor prognosis. Second, we addressed the possibility that concomitant small deletions of the Ph chromosome modulateBCR-ABL transcription. Real-time reverse-transcription polymerase chain reaction was used to demonstrate that derivative chromosome 9 deletions were not accompanied by altered levels of BCR-ABL transcripts. Third, deletions may represent a consequence of genetic instability within the target cell at the time of the Ph translocation, with the poor prognosis reflecting a predisposition to subsequent additional genetic alterations. However, patients with deletions do not exhibit an increased frequency of secondary cytogenetic changes following disease progression. Taken together, these data support a model in which deletions of the derivative chromosome 9 result in rapid disease progression as a result of the loss of one or more genes within the deleted region.

Complex three-way Philadelphia translocation t(6;9;22) (p23;q34;q11.2) along with unusual t(1;4): A chronic myeloid leukemia case report

2018 ◽  
Vol 3 (2) ◽  
pp. 66
Author(s):  
M. Kumar ◽  
Bekleshwar Salona ◽  
Shiv Murti Kumar ◽  
Akshay Gore ◽  
Shivani Sharma
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
International System ◽  
Specific Region ◽  
Chromosome 9 ◽  
Fish Analysis ◽  
Standard Protocol ◽  
The Third ◽  
Ph Chromosome ◽  
Variant Ph Translocation

Chronic myeloid leukemia (CML) is a myeloproliferative disorder and genetically characterized by the presence of the Philadelphia (Ph) chromosome, resulting from a balanced reciprocal translocation between chromosome 9 and 22 at bands 9q34 and 22q11.2 [t(9;22)(q34;q11.2)]. In the formation of the Ph chromosome, the specific region of the ABL oncogene is transposed from 9q34 to the specific region of the BCR gene on chromosome 22 to form a fusion gene BCR‑ABL, which encodes a constitutively active protein, with tyrosine kinase activity. Vast majority of CML patients show classical Ph translocation, t(9;22) and 5–10% of cases are observed with variant Ph translocation. In variant Ph translocation, generally, the third chromosome involved with chromosome 9 and 22. The segment of the third chromosome usually translocates to the chromosome 9 at band 9q34. The formation of variant or complex Ph translocation is controversial topic. A wide array of additional chromosome involved in translocation with the t(9;22) has been described previously in CML patients. In this report, we present a unique and complex Ph translocation involving three chromosomes (6;9;22) in a 25-year-old female 66who was clinically diagnosed as CML. Chromosome analysis using 24 h and 48 h unstimulated culture with GTG-banding was performed according to standard protocol. A total of 20 metaphases analyzed from the bone marrow culture of the patient and karyotyping was performed on the basis of International System for Human Cytogenetic Nomenclature (2016). The FISH analysis was performed according to the standard protocol from sample for confirmation of BCR/ABL gene using dual color fusion FISH probe (Zytovision Probe). All cell’s images were captured using Olympus fluorescent microscope BX-61 equipped with a CCD camera and analyzed using Bioview FISH software.

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