Korean J Lab Med.  2009 Oct;29(5):379-383. 10.3343/kjlm.2009.29.5.379.

Detection of PML/RARA Rearrangement by Reverse Transcriptase-PCR and Sequencing in a Case of Microgranular Acute Promyelocytic Leukemia Lacking t(15;17) on Karyotype and FISH

  • 1Department of Laboratory Medicine, Dong-A University College of Medicine, Busan, Korea. jyhan@dau.ac.kr
  • 2Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea.


We report a case of morphologically microgranular acute promyelocytic leukemia with PML/RARA fusion transcripts demonstrated by reverse transcriptase-PCR and cDNA sequencing, and no PML/RARA fusion detected by karyotype and FISH analyses. Karyotype was 47,XX,+8[19]/46,XX[1]. Although the newer FISH probes provide more accurate detections of t(15;17), it would be necessary to perform other molecular tests to further identify the masked PML/RARA fusions.


Cryptic PML/RARA rearrangement; Acute promyelocytic leukemia; RT-PCR; PML/RARA; Trisomy 8

MeSH Terms

Chromosomes, Human, Pair 15/*genetics
Chromosomes, Human, Pair 17/*genetics
Chromosomes, Human, Pair 8
In Situ Hybridization, Fluorescence/methods
Leukemia, Promyelocytic, Acute/diagnosis/*genetics/pathology
Middle Aged
Oncogene Proteins, Fusion/*genetics
Reverse Transcriptase Polymerase Chain Reaction/*methods
Sequence Analysis, DNA/*methods
*Translocation, Genetic


  • Fig. 1. Abnormal hypogranular or sparsely granular promyelocytes from the peripheral blood smear (A) and bone marrow aspiration smear (B) (Wright-Giemsa stain, ×1,000).

  • Fig. 2. Giemsa-banded karyotype of bone marrow showing a 47,XX,+8. Trisomy 8 (arrow), and intact chromosomes 15 and 17 are observed.

  • Fig. 3. (A) Cohybridization FISH analysis with LSI PML/RARA dual color, dual fusion and chromosome 8 centromeric probes. There are three pink fluorescences on each chromosome 8 centromere, but no PML/RARA fusion signals on metaphase. (B) Cohybridization FISH analysis with LSI RARA dual color, break apart rearrangement and chromosome 8 centromeric probes. There are three chromosomes 8 but no RARA break apart rearrangement signals on metaphase.

  • Fig. 4. RT-PCR for PML/RARA fusion transcripts. S-form (393 bp) PML/RARA chimeric transcripts were amplified. Abbreviation: RT-PCR, reverse transcriptase-PCR.

Cited by  1 articles

핵형분석에서 t(15;17) 결여된 치료관련 급성전골수구성백혈병 1예 보고
Jun Lee, Young-Eun Kim
Lab Med Online. 2021;11(3):211-213.    doi: 10.47429/lmo.2021.11.3.211.


1.Han JY., Kim KE., Kim KH., Park JI., Kim JS. Identification of PML-RARA rearrangement by RT-PCR and sequencing in an acute pro-myelocytic leukemia without t(15;17) on G-banding and FISH. Leuk Res. 2007. 31:239–43.
2.Huh J., Moon H., Chi H., Chung W. Acute promyelocytic leukemia with i(17)(q10) on G-banding and PML/RARA rearrangement by RT-PCR without evidence of PML/RARA rearrangement on FISH. Int J Lab Hematol. 2009. 31:372–4.
3.Brockman SR., Paternoster SF., Ketterling RP., Dewald GW. New highly sensitive fluorescence in situ hybridization method to detect PML/RARα fusion in acute promyelocytic leukemia. Cancer Genet Cytogenet. 2003. 145:144–51.
4.Grimwade D., Biondi A., Mozziconacci MJ., Hagemeijer A., Berger R., Neat M, et al. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Français de Cytogénétique Hématologique, Groupe de Français d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action “Molecular Cytogenetic Diagnosis in Haematological Malignancies”. Blood. 2000. 96:1297–308.
5.Kim M., Lim J., Kim Y., Han K., Lee DH., Chung NG, et al. The genetic characterization of acute promyelocytic leukemia with cryptic t(15;17) including a new recurrent additional cytogenetic abnormality i(17)(q10). Leukemia. 2008. 22:881–3.
6.Wan TS., So CC., Hui KC., Yip SF., Ma ES., Chan LC. Diagnostic utility of dual fusion PML/RARalpha translocation DNA probe (D-FISH) in acute promyelocytic leukemia. Oncol Rep. 2007. 17:799–805.
7.Yamamoto K., Hamaguchi H., Kobayashi M., Tsurukubo Y., Nagata K. Terminal deletion of the long arm of chromosome 9 in acute promyelocytic leukemia with a cryptic PML/RARα rearrangement. Cancer Genet Cytogenet. 1999. 113:120–5.
8.Emillia G., Marasca R., Longo G., Ferrari MG., Notohamiprodjo M., Temperani P, et al. Detection of PML-RARα fusion transcript in Ph positive leukemia with acute promyelocytic phenotype lacking the t(15;17) cytogenetic abnormality. Cancer Genet Cytogenet. 1995. 80:95–9.
9.Degos L., Dombret H., Chomienne C., Daniel MT., Micléa JM., Chastang C, et al. All-trans-retinoic acid as a differentiating agent in the treatment of acute promyelocytic leukemia. Blood. 1995. 85:2643–53.
10.Johansson B., Mertens F., Mitelman F. Secondary chromosomal abnormalities in acute leukemia. Leukemia. 1994. 8:953–62.
11.Fusita K., Oba R., Harada H., Mori H., Niikura H., Isoyama K, et al. Cytogenetics, FISH, and RT-PCR analysis of acute promyelocytic leukemia: structure of the fusion point in a case lacking classic t(15;17) translocation. Leuk Lymphoma. 2003. 44:111–5.
12.Ikeda K., Sasaki K., Tasaka T., Nagai M., Kawanishi K., Takahara J, et al. Detection of PML-retinoic acid receptor-α fusion transcripts in acute promyelocytic leukemia with trisomy 8 but without t(15;17). Am J Hematol. 1994. 45:212–6.
13.Berger R., Bernheim A., Daniel MT., Valensi F., Flandrin G. Cytological types of mitoses and chromosome abnormalities in acute leukemia. Leuk Res. 1983. 7:221–36.
14.Schoch C., Schnittger S., Kern W., Lengfelder E., Löffler H., Hiddemann W, et al. Rapid diagnostic approach to PML-RARalpha-positive acute promyelocytic leukemia. Hematol J. 2002. 3:259–63.
15.Kim KH., Won JH., Jeung KJ., Lee SC., Kim HJ., Bae SB, et al. Novel PML-RARA fusion gene on chromosome 17 in acute promyelocytic leukemia with normal chromosome 15 and 17. Korean J Hematol. 2007. 42:296–300. (김경하, 원종호, 정기주, 이상철, 김현정, 배상명등. 정상핵형을보인급성전골수구백혈병환자의17번염색체에서발견된 PML-RARA 융합유전자. 대한혈액학회지 2007;42:296-300.).
16.Oh SJ., Kim H., Ahn MJ., Kim IS., Jeong TJ., Choi IY, et al. A case of acute promyelocytic leukemia with 46, XX, del(5)(q23)/47, XX, del(5)(q23), +8 but without (15;17) translocation. Korean J Hematol. 2000. 35:174–8. (오석중, 김혁, 안명주, 김인순, 정태준, 최일영등. t(15;17) 전위동반없이 46, XX, del(5)(q23)/47, XX, del(5)(q23),+8 염색체이상을보인급성전골수구성백혈병 (M3) 11예. 대한혈액학회지2 2000;35:174-8.).
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