Clathrin Assembly Lymphoid Myeloid Leukemia-AF10-positive Acute Leukemias: A Report of 2 Cases with a Review of the Literature

Ji Young Huh; Soie Chung; Doyeun Oh; Myung Seo Kang; Hyeon-Seok Eom; Eun Hae Cho; Mi Hwa Han; Sun-Young Kong

doi:10.3343/kjlm.2010.30.2.117

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Huh, Chung, Oh, Kang, Eom, Cho, Han, and Kong: Clathrin Assembly Lymphoid Myeloid Leukemia-AF10-positive Acute Leukemias: A Report of 2 Cases with a Review of the Literature

Case Report

Korean J Leg Med 2010;30(2):117-121.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.2.117

Clathrin Assembly Lymphoid Myeloid Leukemia-AF10-positive Acute Leukemias: A Report of 2 Cases with a Review of the Literature

Ji Young Huh, M.D.¹, Soie Chung, M.D.², Doyeun Oh, M.D.³, Myung Seo Kang, M.D.⁴, Hyeon-Seok Eom, M.D.^5,⁶, Eun Hae Cho, M.D.⁷, Mi Hwa Han, M.S.⁵, Sun-Young Kong, M.D.^5,⁸

¹Department of Laboratory Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Korea

²Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea

³Departments of Internal Medicine and Laboratory Medicine, Seoul, Korea

⁴CHA Gangnam Medical Center, CHA University, Seoul, Korea

⁵Hematologic Malignancies Branch, Research Institute and Hematology Oncology Clinic, Goyang, Korea

⁶National Cancer Center, Goyang, Korea

⁷Greencross Reference Laboratory, Yongin, Korea

⁸Department of Laboratory Medicine, National Cancer Center, Goyang, Korea

Corresponding author: Sun-Young Kong, M.D., Ph.D. Hematologic Malignancies Branch, Division of Translational & Clinical Research II, Research Institute and Department of Laboratory Medicine, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 410-769, Korea Tel: +82-31-920-1735 Fax: +82-31-920-1738 E-mail: ksy@ncc.re.kr

^∗ This work was supported by the National Cancer Center of Korea (Grant No.0810440).

Revised 25 July 20099 March 2010 Accepted 9 March 2010

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

The translocation t(10;11)(p13;q14q21) has been found to be recurrent in acute lymphoblastic and myeloid leukemias, and results in the fusion of the clathrin assembly lymphoid myeloid leukemia (CALM) gene with the AF10 gene; these genes are present on chromosomes 11 and 10, respectively. Because the CALM-AF10 rearrangement is a rare chromosomal abnormality, it is not included in routine molecular tests for acute leukemia. Here, we describe the cases of 2 patients with the CALM-AF10 fusion gene. The first patient (case 1) was diagnosed with T-cell ALL, and the second patient (case 2) was diagnosed with AML. Both patient samples showed expression of the homeobox A gene cluster and the histone methyltransferase hDOT1L, which suggests that they mediate leukemic transformation in CALM-AF10-positive and mixed-lineage leukemia-AF10-positive leukemias. Both patients achieved complete remission after induction chemotherapy. The first patient (case 1) relapsed after double-unit cord blood transplantation; there was no evidence of relapse in the second patient (case 2) after allogenic peripheral blood stem cell transplantation. Since CALM-AF10-positive leukemias have been shown to have poor prognosis with conventional therapy, molecular tests for CALM-AF10 rearrangement would be necessary to detect minimal residual disease during follow-up.

Keywords: t(10;11), CALM-AF10, HOXA gene, hDOT1L, Acute leukemia, Reverse transcriptase-PCR

REFERENCES

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Fig. 1.

Bone marrow aspiration shows several lymphoblasts in the first patient (case 1) (A) and myeloblasts in the second patient (case 2) (B) characterized by medium-sized nuclei and prominent nucleoli (Wright-Giemsa stain, ×1,000).

Fig. 2.

Detection of the CALM-AF10 fusion transcript by RT-PCR in bone marrow cells from cases 1 and 2 and the U937 cell line. A CALM-AF10 fusion transcript of 424 bp was identified in samples of the first (case 1) (A) and second (case 2) (B) patients. Lane M: size marker; lane 1: U937 cell line; lanes 2-4: first patient (case 1) at diagnosis, hematologic remission, and relapse, respectively; lane 5; second patient (case 2) at diagnosis.

Abbreviation: CALM-AF10, clathrin assembly lymphoid myeloid leukemia-AF10.

Fig. 3.

Detection of the HOXA cluster gene and hDOT1L gene expression by RT-PCR in bone marrow cells from cases 1 and 2 and the U937 cell line. Lane 1: U937 cell line; lanes 2-4: first patient (case 1) at diagnosis, hematologic remission and relapse, respectively; lane 5: second patient (case 2) at diagnosis.

Abbreviations: HOXA, homeobox A; hDOT1L, human DOT1-like, histone H3 methyltransferase.

Table 1.

Primers used in PCR amplification

Name	Sequence
HOXA5_F	5′-GTCCACGCACTCTCCTCAG-3′
HOXA5_R	5′-CTTCATTCTCCGGTTTTGGA-3′
HOXA7_F	5′-TCAACAGCCCCCTTTATCAG-3′
HOXA7_R	5′-GCTCTTTCTTCCACTTCATGC-3′
HOXA9_F	5′-TAAACCTGAACCGCTGTCG-3′
HOXA9_R	5′-CATTTTCATCCTGCGGTTCT-3′
HOXA10_F	5′-GCTACTTCCGCCTTTCTCAG-3′
HOXA10_R	5′-GACGCTGCGGCTAATCTCTA-3′
hDOT1L_F	5′-CAAGTTCTCGCTGCCTCACT-3′
hDOT1L_R	5′-GTCCTGAGGGCTCAGCTTC-3′

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