Amplification of BCR–ABL and t(3;21) in a patient with blast crisis of chronic myelogenous leukemia

Phan, Chia Wei; Baharuddin, Puteri J.N.B. Megat; Chin, Lai-Peng; Zakaria, Zubaidah; Yegappan, Subramanian; Sathar, Jameela; Tan, Sen-Mui; Purushothaman, Visalachy; Chang, Kian-Meng

doi:10.1016/j.cancergencyto.2007.09.014

Cited by 12 publications

(10 citation statements)

References 21 publications

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“…First, there was a duplication of the der(8)t(8;22), which could be compared with the duplication of der(9)t(9;22) occurring in 30% of blast crisis CML (Johansson et al, 2002;Schoch et al, 2003;Radich, 2007). Second, the acquisition of a t(3;21)(q26;q22) has been described in a smaller subset of advanced CML (De Braekeleer et al, 2007;Phan et al, 2008). It is of interest to note that RUNX1 altera- Figure 1.…”

mentioning

confidence: 97%

Chronic myeloproliferative disorder with t(8;22)(p11;q11) can mime clonal cytogenetic evolution of authentic chronic myelogeneous leukemia

Richebourg

Theisen

Plantier

et al. 2008

Genes Chromosomes & Cancer

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mentioning

confidence: 97%

Chronic myeloproliferative disorder with t(8;22)(p11;q11) can mime clonal cytogenetic evolution of authentic chronic myelogeneous leukemia

Richebourg

Theisen

Plantier

et al. 2008

Genes Chromosomes & Cancer

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“…The occurrence of t (3; 21) translocation together with amplification of BCR-ABL marks the aggressiveness of disease progression [2]. Animal data demonstrate that bone marrow cells co-transfected with BCR-ABL1 and AME rapidly induce an AML-like malignancy in mice.…”

Section: Discussionmentioning

confidence: 89%

“…It has been previously demonstrated that in t (3;21)-associated leukemia [2] and the fusion of AML1 with MDS1 may interfere with The patient passed away under the treatment due to unknown reasons (Table 1). All derivative chromosomes are marked by highlighted by arrow heads.…”

Section: Discussionmentioning

confidence: 99%

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Cytogenetic Evolution in a Patient with Chronic developing a Secondary Acute Myelogenous Leukemia Subtype M5 Resistant to Imatinib Mesylate Therapy

Moassass¹

2013

J Leuk

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Here we report an unusual case of Chronic Myelogeneous Leukemia (CML) developing towards an Acute Myelogeneous Leukemia subtype M5 (AML-M5). The chromosomal constitution was at (final) stage of AML-M5: Philadelphia chromosome positivity with multiple trisomies, a double t (9; 22) (q34; q11) and an AML1/MDS1/EVI1 (AME) fusion transcript resulting from a t (3; 21) (q26; q22). The latter translocation was detectable first in blast phase of CML and remained present in AML-M5 stage. Overall, four chromosomal analyses were done within 19 months, describing the ongoing karyotypic evolution during this transformation. Unfortunately this exceptional patient did not respond to Imatinib-(IM) or Nilotinib-therapy. These finding May by a first hint that CML-patients acquiring a t (3; 21) (q26; q22) might be appropriate to bone marrow transplantation rather than for IM-therapy.including a double t (9; 22) (q34; q11) and an AME fusion transcript resulting from a t(3;21)(q26;q22).

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“…The additional Ph chromosome houses a second copy of the BCR/ABL1 fusion resulting in genomic amplification of the chimeric gene. In addition, extra copies of the fusion gene have also been described housed by isochromosomes derived from the Ph chromosome or marker structures containing tandem duplications of BCR/ABL1 fusion [5-8]. Moreover, a study using bacterial artificial chromosome (BAC) array comparative genomic hybridization on CML cell lines and patients [9] revealed unexpected gains of the 9q34 region affecting BCR/ABL1 fusion and part of the sequences telomeric to the fusion gene, which could not be explained as due to a simple duplication of the Ph chromosome.…”

Section: Introductionmentioning

confidence: 99%

Genomic amplification of BCR/ABL1 and a region downstream of ABL1 in chronic myeloid leukaemia: a FISH mapping study of CML patients and cell lines

Virgili

Nacheva

2010

Mol Cytogenet

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BackgroundChronic myeloid leukaemia (CML) is characterized by the expression of the BCR/ABL1 fusion gene, a constitutively activated tyrosine kinase that commonly results from the formation of the Philadelphia (Ph) chromosome after a t(9;22)(q34;q11) or variant rearrangement. The duplication of the Ph chromosome is a recurring abnormality acquired during disease progression, whereas intrachromosomal amplification of BCR/ABL1 is a rare phenomenon and has been associated with imatinib therapy resistance. Archival bone marrow chromosome suspensions from 19 CML patients known to carry more than 1 copy of BCR/ABL1 and 10 CML cell lines were analyzed by fluorescent in situ hybridization with a panel of probes from 9q34.1-qter to investigate whether they carried two identical copies of the Ph chromosome or, instead, one or both Ph contained cryptic imbalances of some regions.ResultsA duplication of the entire Ph chromosome with no further events involving the derivative 22 was found in 12 patients. In contrast, a sideline with either 1 or 2 isochromosomes of the Ph chromosome was identified in 6 patients but none of the cell lines. In one of the patients a translocation between the distal end of one arm of the isoderivative chromosome 22 and a third chromosome was revealed. 2 patients were found to carry marker structures harbouring high copy number gains of BCR/ABL1 fusion along with a variable part of 9q34 region downstream of ABL1 breakpoint, similarly to the markers present in the imatinib resistant cell line K562. We identified the following regions of amplification: 9q34.1 → q34.2 and 9q34.1 → qter, with a common minimum amplified region of 682 Kb. One of the patients had 5 BCR/ABL1 positive clones with variable level of 9q34 amplifications on a variety of structures, from an isoderivative 22 to tandem duplications.ConclusionsThese data confirm that the intrachromosomal genomic amplification of BCR/ABL1 that occurs in some CML patients during disease progression also involves amplification of 9q34 gene-rich sequences downstream of ABL1 breakpoint. The variety of rearrangements identified in this relatively small cohort demonstrates that the Ph chromosome is not a stable structure but prone to further rearrangements during disease progression.

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Amplification of BCR–ABL and t(3;21) in a patient with blast crisis of chronic myelogenous leukemia

Cited by 12 publications

References 21 publications

Chronic myeloproliferative disorder with t(8;22)(p11;q11) can mime clonal cytogenetic evolution of authentic chronic myelogeneous leukemia

Chronic myeloproliferative disorder with t(8;22)(p11;q11) can mime clonal cytogenetic evolution of authentic chronic myelogeneous leukemia

Cytogenetic Evolution in a Patient with Chronic developing a Secondary Acute Myelogenous Leukemia Subtype M5 Resistant to Imatinib Mesylate Therapy

Genomic amplification of BCR/ABL1 and a region downstream of ABL1 in chronic myeloid leukaemia: a FISH mapping study of CML patients and cell lines

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