Journal List > Korean J Lab Med > v.29(5) > 1011571

TOOLS
Chang, Park, Lee, Park, Kim, Kim, Han, and Cho: Two Cases of Acute Myeloid Leukemia with t(16;21)(p11;q22) and TLS/FUS-ERG Fusion Transcripts
Case Report

Korean J Leg Med 2009;29(5):390-395.

Published online: 14 January 2009

DOI: https://doi.org/10.3343/kjlm.2009.29.5.390

Two Cases of Acute Myeloid Leukemia with t(16;21)(p11;q22) and TLS/FUS-ERG Fusion Transcripts

Woong Rin Chang, M.D.1, Il Joong Park, M.D.1, Hyun Woo Lee, M.D.2, Joon Seong Park, M.D.2, Hugh Chul Kim, M.D.2, Hyon Joo Kim, M.D.3, Jae Ho Han, M.D.4, Sung Ran Cho, M.D.1

1Departments of Laboratory Medicine, Hematology-Oncology, Suwon, Korea

2Departments of Medical Genetics, Suwon, Korea

3Departments of Pathology, Suwon, Korea

4Ajou University School of Medicine, Suwon, Korea

Corresponding author: Sung Ran Cho, M.D. Department of Laboratory Medicine, Ajou University School of Medicine, San-5 Wonchon-dong, Yeongtong-gu, Suwon 443-721, Korea Tel: +82-31-219-5780, Fax: +82-31-219-5778 E-mail: sungran@ajou.ac.kr

      Revised 29 January 200910 August 2009       Accepted 24 August 2009

Copyright © 2009 Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Many AML-associated chromosomal abnormalities, such as t(8;21), t(15;17), inv(16), t(9;11), t(9;22) and t(6;9) are well known. The chromosomal aberration of t(16;21)(p11;q22) in AML is rare and it is known to be associated with poor prognosis, young age (median age, 22 yr), and involvement of various subtypes of the French-American-British classification. We report here 2 AML patients with t(16;21)(p11;q22), proved by conventional cytogenetics and/or reverse transcription (RT)-PCR. Erythrophagocytosis by leukemic blasts was observed in both of the cases. One patient was a 24 yr-old male with acute myelomonocytic leukemia. His karyotype was 46,XY,t(16;21)(p11;q22),del(18)(p11.2) and RT-PCR revealed the TLS/FUS-ERG fusion transcripts. Although he received allogeneic peripheral blood stem cell transplantation after the first remission, he died 9 months after the initial diagnosis due to relapse of the disease and graft-versus-host disease. The other patient was a 72 yr-old male with acute myeloid leukemia without maturation. His karyotype was 45,XY,-16,add(21)(q22) and the presence of t(16;21)(p11;q22) was detected by RT-PCR. He was transferred to another hospital with no more follow-up. We suggest that the presence of t(16;21)(p11;q22) and/or TLS/FUS-ERG fusion transcripts has to be considered in cases of AML with erythrophagocytosis.

Keywords: Acute myeloid leukemia, t(16;21)(p11;q22), Erythrophagocytosis, TLS/FUS-ERG

REFERENCES

1.Ferro MR., Cabello P., Garcia-Sagredo JM., Resino M., San Roman C., Larana JG. t(16;21) in a Ph positive CML. Cancer Genet Cytogenet. 1992. 60:210–1.
crossref
2.Kanazawa T., Ogawa C., Taketani T., Taki T., Hayashi Y., Morikawa A. TLS/FUS-ERG fusion gene in acute lymphoblastic leukemia with t(16;21)(p11;q22) and monitoring of minimal residual disease. Leuk Lymphoma. 2005. 46:1833–5.
3.Shimizu K., Ichikawa H., Tojo A., Kaneko Y., Maseki N., Hayashi Y, et al. An ets-related gene, ERG, is rearranged in human myeloid leukemia with t(16;21) chromosomal translocation. Proc Natl Acad Sci USA. 1993. 90:10280–4.
4.Ichikawa H., Shimizu K., Hayashi Y., Ohki M. An RNA-binding protein gene, TLS/FUS, is fused to ERG in human myeloid leukemia with t(16;21) chromosomal translocation. Cancer Res. 1994. 54:2865–8.
5.Kong XT., Ida K., Ichikawa H., Shimizu K., Ohki M., Maseki N, et al. Consistent detection of TLS/FUS-ERG chimeric transcripts in acute myeloid leukemia with t(16;21)(p11;q22) and identification of a novel transcript. Blood. 1997. 90:1192–9.
6.Imashuku S., Hibi S., Sako M., Lin YW., Ikuta K., Nakata Y, et al. Hemophagocytosis by leukemic blasts in 7 acute myeloid leukemia cases with t(16;21)(p11;q22): common morphologic characteristics for this type of leukemia. Cancer. 2000. 88:1970–5.
7.Choi HW., Shin MG., Sawyer JR., Cho D., Kee SJ., Baek HJ, et al. Unusual type of TLS/FUS-ERG chimeric transcript in a pediatric acute myelocytic leukemia with 47,XX,+10,t(16;21)(p11;q22). Cancer Genet Cytogenet. 2006. 167:172–6.
8.Perrotti D., Bonatti S., Trotta R., Martinez R., Skorski T., Salomoni P, et al. TLS/FUS, a pro-oncogene involved in multiple chromosomal translocations, is a novel regulator of BCR/ABL-mediated leukemogenesis. EMBO J. 1998. 17:4442–55.
9.Prasad DD., Ouchida M., Lee L., Rao VN., Reddy ES. TLS/FUS fusion domain of TLS/FUS-erg chimeric protein resulting from the t(16;21)chromosomal translocation in human myeloid leukemia functions as a transcriptional activation domain. Oncogene. 1994. 9:3717–29.
10.Imashuku S., Hibi S., Kuriyama K., Todo S. Hemophagocytosis by leukemic blasts in a case of acute megakaryoblastic leukemia with t(16;21)(p11;q22). Int J Hematol. 1999. 70:36–9.
11.Shikami M., Miwa H., Nishii K., Tkahashi T., Shiku H., Tsutani H, et al. Myeloid differentiation antigen and cytokine receptor expression on acute myelocytic leukaemia cells with t(16;21)(p11;q22): frequent expression of CD56 and interleukin-2 receptor α chain. Br J Haematol. 1999. 105:711–9.
12.Jekarl DW., Kim YG., Lim JY., Kim MS., Han KJ., Lee AW, et al. CD56 expression and hemophagocytosis of leukemic cells in acute myeloid leukemia with t(16;21)(p11;q22). Korean J Lab Med. 2008. 28(S2):S371.
13.Swerdlow SH, Campo E, editors. WHO classification of tumors of haematopoietic and lymphoid tissues. 4th ed.Lyon: International Agency for Research on Cancer;2008. p. 137.
14.Perot C., Huret JL. Atlas of genetics and cytogenetics in oncology and haematology. http://AtlasGeneticsOncology.org/Anomalies/t1621.html. (Updated on Jan. 2005.

Fig. 1.
Bone marrow smears of case 1 (A) and case 2 (B) showing blast cells with erythrophagocytic activity and cytoplasmic vacuoles (Wright-Giemsa stain, ×1,000).
kjlm-29-390f1.tif
Fig. 2.
Karyograms of the patients presented. (A) Case 1 showing 46,XY,t(16;21)(p11;q22),del(18)(p11.2). (B) Case 2 showing 45,XY, −16,add(21)(q22). Arrows indicate rearranged and abnormal chromosomes.
kjlm-29-390f2.tif
Fig. 3.
(A) Multiplex RT-PCR using HemaVision kit in case 1 (upper) and case 2 (lower). Both show an internal control band (911 bp, arrowhead) in each lane and 2 unknown bands (1 strong, 1 weak) in lane 5. (B) RT-PCR for t(16;21)(p11;q22) using HemaVision split-out PCR kit. Both cases show bands for the internal control (911 bp, arrowhead) and the TLS/FUS-ERG fusion transcripts of type A (313 bp) and type B (269 bp). Lane 1, 100 bp ladder; lane 2, case 1; lane 3, case 2. (C) RT-PCR for t(16;21)(p11;q22) using the primers reported by Kong, et al. Both cases have type A (255 bp), type B (211 bp), and an extra band (∗). Lane 1, 100 bp ladder; lane 2, negative control; lane 3, case 1; lane 4, case 2.
kjlm-29-390f3.tif
Table 1.
Clinical and hematological characteristics of 2 AML patients with t(16;21)(p11;q22)
No. Case 1 2
Age/sex 24/M 72/M
Subtype Acute myelomonocytic leukemia AML without maturation
Survival (months) 9 1+∗
WBC (/μL) 7,700 2,300
Hb (g/dL) 4.5 8.5
Platelets (/μL) 10,000 124,000
% Blasts    
Peripheral blood 84 29
Bone marrow 58 48
Immunophenotype (% positive cells) CD13 (46) CD13 (30)
  CD14 (23) CD33 (75)
  CD33 (89) CD34 (76)
  CD34 (66) CD61 (20)
  HLA-DR (40) HLA-DR (21)
Cytochemical stain    
SBB + -
PAS - -
ANBE + -
Immunohistochemical stain (additional)    
CD56 - -
MPO ND +
vWF ND -

∗ Follow-up was not possible after one month.

Abbreviations: WBC, white blood cells; SBB, Sudan black B; PAS, periodic acid-Schiff; ANBE, α-naphtyl butyrate esterase; MPO, myeloper-oxidase; vWF, von Willebrand factor; ND, not done.

TOOLS
Similar articles