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High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA.

Powers B, Persons D, Rao D, Woodroof J, Lin TL - Case Rep Hematol (2015)

Bottom Line: Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given.The patient remains on maintenance therapy and remains in remission.This is the first such report of a 5-way chromosomal translocation leading to APL.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66210, USA.

ABSTRACT
Acute promyelocytic leukemia (APL) is classically characterized by chromosomal translocation (15;17), resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17) which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.

No MeSH data available.


Related in: MedlinePlus

(a) Metaphase FISH: dual-color dual-fusion FISH probe has one fusion, two orange (PML) and two green (RARA) signals on representative metaphase nuclei. (b) Illustration of positions of FISH probes based on several DAPI (as in (a)) and reverse DAPI (not shown) metaphase studies confirming the complex translocation: t(9;17;15;12;15)(q34;q21;q24;q13;q26.1).
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fig2: (a) Metaphase FISH: dual-color dual-fusion FISH probe has one fusion, two orange (PML) and two green (RARA) signals on representative metaphase nuclei. (b) Illustration of positions of FISH probes based on several DAPI (as in (a)) and reverse DAPI (not shown) metaphase studies confirming the complex translocation: t(9;17;15;12;15)(q34;q21;q24;q13;q26.1).

Mentions: The bone marrow aspirate and biopsy showed a hypercellular marrow (90–100% cellular with 64% blasts) and decreased trilineage hematopoiesis (Figure 1(b)). Butyrate esterase stain was negative for monocytic differentiation. Flow cytometry showed blasts comprising 92% of total cells, positive for dim CD2 (aberrant), dim CD4 (aberrant), CD13, CD33, CD34, dim CD38, CD56 (aberrant), CD64, CD117, partial HLA-DR, and myeloperoxidase. Fluorescence in situ hybridization (FISH) using probes for the PML (15q24.1) and RARA (17q21.1) regions showed a signal pattern consistent with PML/RARA rearrangement and a complex translocation involving t(15;17) in all 200 nuclei assessed (Figure 2(a)). FISH using a chromosome 17 probe and ABL1 probe confirmed that a portion of 9q was present on the derivative chromosome 17 (not shown). Conventional cytogenetics revealed that 18 of 20 metaphases had a complex translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. The final karyotype was 46,XY,t(9;17;15;12;15)(q34;q21;q24;q13;q26.1)[18]/46,XY[2] (Figure 2(b)).


High-Risk Microgranular Acute Promyelocytic Leukemia with a Five-Way Complex Translocation Involving PML-RARA.

Powers B, Persons D, Rao D, Woodroof J, Lin TL - Case Rep Hematol (2015)

(a) Metaphase FISH: dual-color dual-fusion FISH probe has one fusion, two orange (PML) and two green (RARA) signals on representative metaphase nuclei. (b) Illustration of positions of FISH probes based on several DAPI (as in (a)) and reverse DAPI (not shown) metaphase studies confirming the complex translocation: t(9;17;15;12;15)(q34;q21;q24;q13;q26.1).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321077&req=5

fig2: (a) Metaphase FISH: dual-color dual-fusion FISH probe has one fusion, two orange (PML) and two green (RARA) signals on representative metaphase nuclei. (b) Illustration of positions of FISH probes based on several DAPI (as in (a)) and reverse DAPI (not shown) metaphase studies confirming the complex translocation: t(9;17;15;12;15)(q34;q21;q24;q13;q26.1).
Mentions: The bone marrow aspirate and biopsy showed a hypercellular marrow (90–100% cellular with 64% blasts) and decreased trilineage hematopoiesis (Figure 1(b)). Butyrate esterase stain was negative for monocytic differentiation. Flow cytometry showed blasts comprising 92% of total cells, positive for dim CD2 (aberrant), dim CD4 (aberrant), CD13, CD33, CD34, dim CD38, CD56 (aberrant), CD64, CD117, partial HLA-DR, and myeloperoxidase. Fluorescence in situ hybridization (FISH) using probes for the PML (15q24.1) and RARA (17q21.1) regions showed a signal pattern consistent with PML/RARA rearrangement and a complex translocation involving t(15;17) in all 200 nuclei assessed (Figure 2(a)). FISH using a chromosome 17 probe and ABL1 probe confirmed that a portion of 9q was present on the derivative chromosome 17 (not shown). Conventional cytogenetics revealed that 18 of 20 metaphases had a complex translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. The final karyotype was 46,XY,t(9;17;15;12;15)(q34;q21;q24;q13;q26.1)[18]/46,XY[2] (Figure 2(b)).

Bottom Line: Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given.The patient remains on maintenance therapy and remains in remission.This is the first such report of a 5-way chromosomal translocation leading to APL.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Internal Medicine, University of Kansas School of Medicine, 3901 Rainbow Boulevard, Kansas City, KS 66210, USA.

ABSTRACT
Acute promyelocytic leukemia (APL) is classically characterized by chromosomal translocation (15;17), resulting in the PML-RARA fusion protein leading to disease. Here, we present a case of a 50-year-old man who presented with signs and symptoms of acute leukemia with concern for APL. Therapy was immediately initiated with all-trans retinoic acid. The morphology of his leukemic blasts was consistent with the hypogranular variant of APL. Subsequent FISH and cytogenetic analysis revealed a unique translocation involving five chromosomal regions: 9q34, 17q21, 15q24, 12q13, and 15q26.1. Molecular testing demonstrated PML/RARA fusion transcripts. Treatment with conventional chemotherapy was added and he went into a complete remission. Given his elevated white blood cell count at presentation, intrathecal chemotherapy for central nervous system prophylaxis was also given. The patient remains on maintenance therapy and remains in remission. This is the first such report of a 5-way chromosomal translocation leading to APL. Similar to APL with chromosomal translocations other than classical t(15;17) which result in the typical PML-RARA fusion, our patient responded promptly to an ATRA-containing regimen and remains in complete remission.

No MeSH data available.


Related in: MedlinePlus