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Genomic amplification of MYC as double minutes in a patient with APL-like leukemia.

Poddighe PJ, Wessels H, Merle P, Westers M, Bhola S, Loonen A, Zweegman S, Ossenkoppele GJ, Wondergem MJ - Mol Cytogenet (2014)

Bottom Line: Fluorescence in situ hybridization (FISH) with DNA probes specific for the MYC-region showed the presence of multiple MYC amplicons.SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region.The diagnosis was revised to AML, not otherwise specified (AML, NOS) and therefore therapy with ATRA was discontinued.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, PK 0X011, Amsterdam, 1081 HV The Netherlands.

ABSTRACT

Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by a PML-RARA fusion due to a translocation t(15;17). Its sensitivity to treatment with all-trans retinoic acid (ATRA), which causes differentiation of the abnormal promyelocytes, combined with anthracycline based chemotherapy makes it the best curable subtype of acute myeloid leukemia. A rapid and accurate diagnosis is needed in the first place to prevent (more) bleeding problems. Here we present a patient with a leukemia with an APL-like morphology but no detectable PML-RARA fusion, as demonstrated by RT-PCR and cytogenetic analysis.

Results: Unexpectedly, karyotyping revealed numerous double minutes (dmins). Fluorescence in situ hybridization (FISH) with DNA probes specific for the MYC-region showed the presence of multiple MYC amplicons. SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region.

Conclusions: The diagnosis was revised to AML, not otherwise specified (AML, NOS) and therefore therapy with ATRA was discontinued.

No MeSH data available.


Related in: MedlinePlus

Cytomorphologic and cytogenetic results. (A) A representative cytomorphologic bone marrow field, showing blasts with Auer rods (arrow) and azurophilic inclusions. (B) A representative metaphase cell demonstrating normal chromosomes 15 and 17, and more than 20 double minutes (red arrowheads). (C) Metaphase FISH of this patient with the ON MYC(green)/IGH(red) t(8;14) Fusion Probe (Kreatech), showing MYC-positive dmins (green), and both chromosomes 14 (arrow); in this cell it was not possible to indicate the normal chromosome 8 due to the high number of dmins (D) Metaphase FISH with a BAC-probe RP1-80K22 (base pair position 128,667,455-128,814,588) for MYC gene (red) and a flanking BAC-probe RP11-125A17 (base pair position 128,865,417-129,036,660; green), demonstrating multiple copies of dmins (red-green signals). Only one chromosome 8 (arrow) contains the MYC gene region.
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Fig1: Cytomorphologic and cytogenetic results. (A) A representative cytomorphologic bone marrow field, showing blasts with Auer rods (arrow) and azurophilic inclusions. (B) A representative metaphase cell demonstrating normal chromosomes 15 and 17, and more than 20 double minutes (red arrowheads). (C) Metaphase FISH of this patient with the ON MYC(green)/IGH(red) t(8;14) Fusion Probe (Kreatech), showing MYC-positive dmins (green), and both chromosomes 14 (arrow); in this cell it was not possible to indicate the normal chromosome 8 due to the high number of dmins (D) Metaphase FISH with a BAC-probe RP1-80K22 (base pair position 128,667,455-128,814,588) for MYC gene (red) and a flanking BAC-probe RP11-125A17 (base pair position 128,865,417-129,036,660; green), demonstrating multiple copies of dmins (red-green signals). Only one chromosome 8 (arrow) contains the MYC gene region.

Mentions: A 76-year-old man presented with exertional dyspnea, visual disturbances, night sweats and progressive fatigue. His medical history showed chronic obstructive pulmonary disease, Diabetes Mellitus type 2, hypercholesterolemia and alcohol abuse. On physical examination he had some petechiae and hematoma on the lower extremities. No lymphadenopathy or organomegaly was found. His white blood cell count was extremely elevated (220 × 109/l). Hemoglobin was 6.5 mmol/l and platelets were 20 × 109/l. The peripheral blood smear revealed 37 × 109/l blasts, with Auer rods, but also 78 × 109/l promyelocytes, with some faggot cells, resembling typical APL (Figure 1A). Other abnormal laboratory findings included a LDH of 5230 U/l and creatinine of 130 micromol/l. No coagulation abnormalities were present.Figure 1


Genomic amplification of MYC as double minutes in a patient with APL-like leukemia.

Poddighe PJ, Wessels H, Merle P, Westers M, Bhola S, Loonen A, Zweegman S, Ossenkoppele GJ, Wondergem MJ - Mol Cytogenet (2014)

Cytomorphologic and cytogenetic results. (A) A representative cytomorphologic bone marrow field, showing blasts with Auer rods (arrow) and azurophilic inclusions. (B) A representative metaphase cell demonstrating normal chromosomes 15 and 17, and more than 20 double minutes (red arrowheads). (C) Metaphase FISH of this patient with the ON MYC(green)/IGH(red) t(8;14) Fusion Probe (Kreatech), showing MYC-positive dmins (green), and both chromosomes 14 (arrow); in this cell it was not possible to indicate the normal chromosome 8 due to the high number of dmins (D) Metaphase FISH with a BAC-probe RP1-80K22 (base pair position 128,667,455-128,814,588) for MYC gene (red) and a flanking BAC-probe RP11-125A17 (base pair position 128,865,417-129,036,660; green), demonstrating multiple copies of dmins (red-green signals). Only one chromosome 8 (arrow) contains the MYC gene region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4228273&req=5

Fig1: Cytomorphologic and cytogenetic results. (A) A representative cytomorphologic bone marrow field, showing blasts with Auer rods (arrow) and azurophilic inclusions. (B) A representative metaphase cell demonstrating normal chromosomes 15 and 17, and more than 20 double minutes (red arrowheads). (C) Metaphase FISH of this patient with the ON MYC(green)/IGH(red) t(8;14) Fusion Probe (Kreatech), showing MYC-positive dmins (green), and both chromosomes 14 (arrow); in this cell it was not possible to indicate the normal chromosome 8 due to the high number of dmins (D) Metaphase FISH with a BAC-probe RP1-80K22 (base pair position 128,667,455-128,814,588) for MYC gene (red) and a flanking BAC-probe RP11-125A17 (base pair position 128,865,417-129,036,660; green), demonstrating multiple copies of dmins (red-green signals). Only one chromosome 8 (arrow) contains the MYC gene region.
Mentions: A 76-year-old man presented with exertional dyspnea, visual disturbances, night sweats and progressive fatigue. His medical history showed chronic obstructive pulmonary disease, Diabetes Mellitus type 2, hypercholesterolemia and alcohol abuse. On physical examination he had some petechiae and hematoma on the lower extremities. No lymphadenopathy or organomegaly was found. His white blood cell count was extremely elevated (220 × 109/l). Hemoglobin was 6.5 mmol/l and platelets were 20 × 109/l. The peripheral blood smear revealed 37 × 109/l blasts, with Auer rods, but also 78 × 109/l promyelocytes, with some faggot cells, resembling typical APL (Figure 1A). Other abnormal laboratory findings included a LDH of 5230 U/l and creatinine of 130 micromol/l. No coagulation abnormalities were present.Figure 1

Bottom Line: Fluorescence in situ hybridization (FISH) with DNA probes specific for the MYC-region showed the presence of multiple MYC amplicons.SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region.The diagnosis was revised to AML, not otherwise specified (AML, NOS) and therefore therapy with ATRA was discontinued.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Genetics, VU University Medical Center, De Boelelaan 1117, PK 0X011, Amsterdam, 1081 HV The Netherlands.

ABSTRACT

Background: Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) characterized by a PML-RARA fusion due to a translocation t(15;17). Its sensitivity to treatment with all-trans retinoic acid (ATRA), which causes differentiation of the abnormal promyelocytes, combined with anthracycline based chemotherapy makes it the best curable subtype of acute myeloid leukemia. A rapid and accurate diagnosis is needed in the first place to prevent (more) bleeding problems. Here we present a patient with a leukemia with an APL-like morphology but no detectable PML-RARA fusion, as demonstrated by RT-PCR and cytogenetic analysis.

Results: Unexpectedly, karyotyping revealed numerous double minutes (dmins). Fluorescence in situ hybridization (FISH) with DNA probes specific for the MYC-region showed the presence of multiple MYC amplicons. SNP-array analysis uncovered amplification of the 8q24.13-q24.21 region, including the MYC-gene, flanked by deletions in 8q24.13 and 8q24.21-q24.22, and a homozygous deletion in 9p21.3, flanked by heterozygous deletions in the same chromosome region.

Conclusions: The diagnosis was revised to AML, not otherwise specified (AML, NOS) and therefore therapy with ATRA was discontinued.

No MeSH data available.


Related in: MedlinePlus