Korean J Lab Med.  2011 Jan;31(1):13-17. 10.3343/kjlm.2011.31.1.13.

A Case of Therapy-related Acute Lymphoblastic Leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 Gene Rearrangement

• Yoo BJ
• Nam MH
• Sung HJ
• Lim CS
• Lee CK
• Cho YJ
• Lee KN
• Yoon SY

• KMID: 1096654
• DOI: http://doi.org/10.3343/kjlm.2011.31.1.13

Abstract

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.

Keyword

MLL gene rearrangement; Secondary leukemia; Therapy-related ALL; Breast cancer

MeSH Terms

Adult
Antineoplastic Agents/therapeutic use
Base Sequence
Breast Neoplasms/drug therapy/radiotherapy
*Chromosomes, Human, Pair 11
*Chromosomes, Human, Pair 19
Combined Modality Therapy
Cyclophosphamide/therapeutic use
Doxorubicin/therapeutic use
Female
Gene Rearrangement
Humans
Immunophenotyping
Karyotyping
Molecular Sequence Data
Myeloid-Lymphoid Leukemia Protein/*genetics
Neoplasm Proteins/*genetics
Nuclear Proteins/*genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma/*diagnosis/genetics
Sequence Analysis, DNA
Tamoxifen/therapeutic use
Transcription Factors/*genetics
*Translocation, Genetic

Figure

• 

  Fig. 1 Morphologic findings of B-ALL in the bone marrow. (A) Bone marrow aspirate smear shows moderate- to large-sized blasts with cytoplasmic vacuolation (Wright-Giemsa stain, ×1,000). (B) Bone marrow biopsy shows almost complete replacement of hypercellular marrow by blasts (hematoxylin and eosin stain, ×100).

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  Fig. 2 G-banding of a bone marrow cell showing a 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16] karyotype.

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  Fig. 3 Interphase FISH using the LSI MLL dual color, break apart rearrangement probe (Abbott) set. Interphase nucleus harboring the MLL translocation, 1 fusion signal, and 2 separate signals (1F1O1G).

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  Fig. 4 MLL1/ENL fusion transcript identified by multiplex reverse transcription-PCR. (A) Amplification products of 8 parallel multiplex reverse transcription-PCR reactions. Two bands (319 bp and 432 bp; arrow heads) are noted in lane 3. (B) Corresponding split-out reactions. Two positive bands in lane D represent the fusion transcript MLL1/ENL [t(11;19)(q23;p13.3)]. (Lanes 1 and A, 100-bp DNA ladder) (C) Part of the sequence from the 319-bp amplicon from lane D shows t(11;19) (q23;p13.3) MLL exon 9/MLLT1 exon 2. (D) Part of the sequence from the 432-bp amplicon from lane D shows t(11;19)(q23;p13.3) MLL exon 10/MLLT1 exon 2; pink, MLL exon 8; yellow, MLL exon 9; blue, MLL exon 10; green, 5' end of MLLT1 exon 2.

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