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

• Huh JY
• Chung S
• Oh D
• Kang MS
• Eom HS
• Cho EH
• Han MH
• Kong SY

• KMID: 1096795
• DOI: http://doi.org/10.3343/kjlm.2010.30.2.117

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.

Keyword

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

MeSH Terms

Adolescent
Adult
Bone Marrow/pathology
Chromosomes, Human, Pair 10
Chromosomes, Human, Pair 11
Cord Blood Stem Cell Transplantation
Female
Histone-Lysine N-Methyltransferase/genetics/metabolism
Homeodomain Proteins/genetics/metabolism
Humans
Leukemia, Myeloid, Acute/diagnosis/*genetics/therapy
Male
Monomeric Clathrin Assembly Proteins/*genetics
Oncogene Proteins, Fusion/*genetics
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/diagnosis/*genetics/therapy
Recurrence
Transcription Factors/*genetics
Translocation, Genetic

Figure

• 

  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).

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  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.

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  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.

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