Korean J Hematol.  2007 Sep;42(3):296-300. 10.5045/kjh.2007.42.3.296.

Novel PML-RARA Fusion Gene on Chromosome 17 in Acute Promyelocytic Leukemia with Normal Chromosome 15 and 17

• Kim KH
• Won JH
• Jeung KJ
• Lee SC
• Kim HJ
• Bae SB
• Kim CK
• Lee NS
• Lee KT
• Park SK
• Hong DS
• Park HS
• Lee YK

• KMID: 2305207
• DOI: http://doi.org/10.5045/kjh.2007.42.3.296

Abstract

We describe a patient with acute promyelocytic leukemia (APL) with no detectable cytogenetic abnormality of either chromosomes 15 or 17 who nevertheless had juxtaposition of promyelocytic leukemia (PML) and retinoic acid receptor-alpha (RARA) and expressed a chimeric transcript. Conventional cytogenetics showed the 46, XX. The metaphase fluorescence in situ hybridization (FISH) with a 5' PML and 3' RARA probe showed a juxtaposed PML-RARA fusion signal on one chromosome 17 homologue, an RARA signals on the other chromosome 17 homologue, and one PML signal on each chromosome 15 homologue. Our patient is presently in remission and doing well after chemotherapy with idarubicin and all trans retinoic acid (ATRA) treatment. Our results show that APL patients with cytogenetically normal chromosome 15 and 17 may, nevertheless, have involvement of both PML and RARA genes and as the prognostic outcome in APL is associated with the presence of a PML-RARA fusion, it is necessary to perform RT-PCR or FISH to aid diagnosis.

Keyword

Acute promyelocytic leukemia; PML-RARA; Insertional translocation

MeSH Terms

Chromosome Aberrations
Chromosomes, Human, Pair 15*
Chromosomes, Human, Pair 17*
Cytogenetics
Diagnosis
Drug Therapy
Fluorescence
Humans
Idarubicin
In Situ Hybridization
Leukemia
Leukemia, Promyelocytic, Acute*
Metaphase
Tretinoin
Idarubicin
Tretinoin

Figure

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  Fig. 1 (A) Bone marrow aspiration cytology. There are several abnormal promyelocytes with intense azurophilic granulation. Several of the promyelocytes contain numerous Auer rods (Faggot cells) (Wrignt-Giemsa stain, ×1,000). (B) G-banded karyotype of bone marrow shows a normal karyotype with apparently normal chromosomes 15 and 17.

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  Fig. 2 (A) Design of the probe for PML-RARA gene detection. (B) Typical FISH for the classical t(15;17) with PML-RARA fusion. FISH probes PML (15q22) and RARA (17q21) demonstrate the presence of a PML-RARA fusion resulting from the 15;17 translocation. Two interphase cells have one separate red (PML) signal, one separate green (RARA) signal and one overlapping red/green signal consistent with the presence of a PML/RARA gene fusion. (C) Interphase FISH for the present case. An interphase cell has one PML-RARA fusion signal, two PML signals and one separate RARA signal. (D) Metaphase FISH for the present case. Metaphase shows two red PML signals on both chromosomes 15, one green RARA signal on one chromosome 17, and one fusion signal on the other chromosome 17.

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  Fig. 3 RT-PCR for PML-RARA gene. Initial RT-PCR having PML-RARA fusion transcript and post-treatment RT-PCR showing PML-RARA negative.

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