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A case of acute myeloid leukemia (AML) with an unreported combination of chromosomal abnormalities: gain of isochromosome 5p, tetrasomy 8 and unbalanced translocation der(19)t(17;19)(q23;p13).

Paar C, Herber G, Voskova D, Fridrik M, Stekel H, Berg J - Mol Cytogenet (2013)

Bottom Line: By using the der(19)t(17;19) as clonal marker, we found that i(5)(p10) and tetrasomy 8 were secondary genetic events and that tetrasomy 8 had clonally evolved from trisomy 8.This case of acute monoblastic leukemia presents a combination of rare chromosomal abnormalities including the unbalanced translocation der(19)t(17;19)(q23;p13.3), hitherto un-reported in AML.Reporting and collecting data of rare chromosomal abnormalities will add information to AML disease, progression and prognosis, and may eventually translate to improved patient management.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Laboratory Medicine, General Hospital Linz, Krankenhausstrasse 9, A-4020, Linz, Austria. joerg.berg@akh.linz.at.

ABSTRACT

Background: Acute myeloid leukemia (AML) comprises a spectrum of myeloid malignancies which are often associated with distinct chromosomal abnormalities, and the analysis of such abnormalities provides us with important information for disease classification, treatment selection and prognosis. Some chromosomal abnormalities albeit recurrent are rare such as tetrasomy 8 or isochromosome 5p. In addition, erratic chromosomal rearrangements may occur in AML, sometimes unbalanced and also accompanied by other abnormalities. Knowledge on the contribution of rare abnormalities to AML disease, progression and prognosis is limited.Here we report a unique case of acute monoblastic leukemia with gain of i(5)(p10), tetrasomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1.

Results: Bone marrow cells were examined by conventional karyotyping, fluorescence in situ hybridization (FISH) and mutation analysis at diagnosis and follow-up. At diagnosis we detected trisomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1. During the course of the disease we observed clonal evolution with gain of i(5)(p10), tetrasomy 8 and eventually duplication of der(19)t(17;19)(q23;p13.3). By using the der(19)t(17;19) as clonal marker, we found that i(5)(p10) and tetrasomy 8 were secondary genetic events and that tetrasomy 8 had clonally evolved from trisomy 8.

Conclusions: This case of acute monoblastic leukemia presents a combination of rare chromosomal abnormalities including the unbalanced translocation der(19)t(17;19)(q23;p13.3), hitherto un-reported in AML. In addition, our case supports the hypothesis of a step-wise clonal evolution from trisomy 8 to tetrasomy 8 in AML. Reporting and collecting data of rare chromosomal abnormalities will add information to AML disease, progression and prognosis, and may eventually translate to improved patient management.

No MeSH data available.


Related in: MedlinePlus

Partial karyograms of clonal evolution. GTG-banded partial karyograms of all the involved chromosomes show the step-wise clonal evolution from trisomy 8 to tetrasomy 8, gain of i(5)(p10) and derivative chromosome(s) 19 in the predominant sideline 1 at diagnosis, at first and second relapse (upper panel). The lower panel depicts sideline 2 with trisomy 8, monosomy 13, a derivative chromosome 19 and three marker chromosomes (second relapse). Note, no other aberrant clones have been detected at the respective time points.
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Figure 1: Partial karyograms of clonal evolution. GTG-banded partial karyograms of all the involved chromosomes show the step-wise clonal evolution from trisomy 8 to tetrasomy 8, gain of i(5)(p10) and derivative chromosome(s) 19 in the predominant sideline 1 at diagnosis, at first and second relapse (upper panel). The lower panel depicts sideline 2 with trisomy 8, monosomy 13, a derivative chromosome 19 and three marker chromosomes (second relapse). Note, no other aberrant clones have been detected at the respective time points.

Mentions: At diagnosis conventional cytogenetics revealed the following karyotype: 47,XY,+8,add(19)(p13)[5]/46,XY[15]. The initial karyotype was defined more precisely with multicolor fluorescence in situ hybridization (24X-FISH) analysis, which yielded to the following karyotype: 47,XY,+8,der(19)t(17;19)(q23;p13.3)[6]/46,XY[19]. At first relapse a marked clonal evolution had occurred with gain of isochromosome 5p and tetrasomy 8. The evolved karyotype was determined as: 49,XY,+i(5)(p10),+8,+8,der(19)t(17;19)(q23;p13.3)[7]/46,XY[14] (Figure 1). At second relapse cytogenetic analysis showed a duplication of the derivative chromosome 19 with loss of the normal chromosome 19 (Figures 1 and 2A). In addition, a second line was detected with trisomy 8, monosomy 13, der(19)t(17;19) and 3 marker chromosomes, however, no i(5)(p10).


A case of acute myeloid leukemia (AML) with an unreported combination of chromosomal abnormalities: gain of isochromosome 5p, tetrasomy 8 and unbalanced translocation der(19)t(17;19)(q23;p13).

Paar C, Herber G, Voskova D, Fridrik M, Stekel H, Berg J - Mol Cytogenet (2013)

Partial karyograms of clonal evolution. GTG-banded partial karyograms of all the involved chromosomes show the step-wise clonal evolution from trisomy 8 to tetrasomy 8, gain of i(5)(p10) and derivative chromosome(s) 19 in the predominant sideline 1 at diagnosis, at first and second relapse (upper panel). The lower panel depicts sideline 2 with trisomy 8, monosomy 13, a derivative chromosome 19 and three marker chromosomes (second relapse). Note, no other aberrant clones have been detected at the respective time points.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3852770&req=5

Figure 1: Partial karyograms of clonal evolution. GTG-banded partial karyograms of all the involved chromosomes show the step-wise clonal evolution from trisomy 8 to tetrasomy 8, gain of i(5)(p10) and derivative chromosome(s) 19 in the predominant sideline 1 at diagnosis, at first and second relapse (upper panel). The lower panel depicts sideline 2 with trisomy 8, monosomy 13, a derivative chromosome 19 and three marker chromosomes (second relapse). Note, no other aberrant clones have been detected at the respective time points.
Mentions: At diagnosis conventional cytogenetics revealed the following karyotype: 47,XY,+8,add(19)(p13)[5]/46,XY[15]. The initial karyotype was defined more precisely with multicolor fluorescence in situ hybridization (24X-FISH) analysis, which yielded to the following karyotype: 47,XY,+8,der(19)t(17;19)(q23;p13.3)[6]/46,XY[19]. At first relapse a marked clonal evolution had occurred with gain of isochromosome 5p and tetrasomy 8. The evolved karyotype was determined as: 49,XY,+i(5)(p10),+8,+8,der(19)t(17;19)(q23;p13.3)[7]/46,XY[14] (Figure 1). At second relapse cytogenetic analysis showed a duplication of the derivative chromosome 19 with loss of the normal chromosome 19 (Figures 1 and 2A). In addition, a second line was detected with trisomy 8, monosomy 13, der(19)t(17;19) and 3 marker chromosomes, however, no i(5)(p10).

Bottom Line: By using the der(19)t(17;19) as clonal marker, we found that i(5)(p10) and tetrasomy 8 were secondary genetic events and that tetrasomy 8 had clonally evolved from trisomy 8.This case of acute monoblastic leukemia presents a combination of rare chromosomal abnormalities including the unbalanced translocation der(19)t(17;19)(q23;p13.3), hitherto un-reported in AML.Reporting and collecting data of rare chromosomal abnormalities will add information to AML disease, progression and prognosis, and may eventually translate to improved patient management.

View Article: PubMed Central - HTML - PubMed

Affiliation: Institute of Laboratory Medicine, General Hospital Linz, Krankenhausstrasse 9, A-4020, Linz, Austria. joerg.berg@akh.linz.at.

ABSTRACT

Background: Acute myeloid leukemia (AML) comprises a spectrum of myeloid malignancies which are often associated with distinct chromosomal abnormalities, and the analysis of such abnormalities provides us with important information for disease classification, treatment selection and prognosis. Some chromosomal abnormalities albeit recurrent are rare such as tetrasomy 8 or isochromosome 5p. In addition, erratic chromosomal rearrangements may occur in AML, sometimes unbalanced and also accompanied by other abnormalities. Knowledge on the contribution of rare abnormalities to AML disease, progression and prognosis is limited.Here we report a unique case of acute monoblastic leukemia with gain of i(5)(p10), tetrasomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1.

Results: Bone marrow cells were examined by conventional karyotyping, fluorescence in situ hybridization (FISH) and mutation analysis at diagnosis and follow-up. At diagnosis we detected trisomy 8, an unbalanced translocation der(19)t(17;19)(q23;p13.3) and mutated NPM1. During the course of the disease we observed clonal evolution with gain of i(5)(p10), tetrasomy 8 and eventually duplication of der(19)t(17;19)(q23;p13.3). By using the der(19)t(17;19) as clonal marker, we found that i(5)(p10) and tetrasomy 8 were secondary genetic events and that tetrasomy 8 had clonally evolved from trisomy 8.

Conclusions: This case of acute monoblastic leukemia presents a combination of rare chromosomal abnormalities including the unbalanced translocation der(19)t(17;19)(q23;p13.3), hitherto un-reported in AML. In addition, our case supports the hypothesis of a step-wise clonal evolution from trisomy 8 to tetrasomy 8 in AML. Reporting and collecting data of rare chromosomal abnormalities will add information to AML disease, progression and prognosis, and may eventually translate to improved patient management.

No MeSH data available.


Related in: MedlinePlus