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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 - Korean J Lab Med (2011)

Bottom Line: The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.

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.

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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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Figure 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).

Mentions: A 40-yr-old woman underwent breast surgery for cancer of the right breast and received 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) and radiation therapy (dose, 5,900 cGy), followed by anticancer endocrine therapy with tamoxifen. Complete blood cell counts obtained at 15 months after chemotherapy indicated acute leukemia: white blood cell count, 3.5 × 109/L with 15% blasts; Hb level, 5.8 g/dL; and platelet count, 31.0 × 109/L. Bone marrow examination showed hypercellular marrow with increased blasts, accounting for up to 95% of all bone marrow nucleated cells (Fig. 1). An immunophenotyping study using flow cytometry revealed that the blasts were positive for CD19, CD34, and cytoplasmic CD79a and negative for CD2, CD3, CD5, CD7, CD10, CD13, CD14, CD20, CD22, CD33, CD41, CD117, and myeloperoxidase. On the basis of the immunophenotype of the blasts, we diagnosed the patient with B-ALL. Cytogenetic analysis of the bone marrow aspirates by using the G-banding revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16] (Fig. 2). FISH performed using LSI MLL dual color, break apart rearrangement probes (Abbott Molecular, Des Plaines, IL, USA) showed an MLL break apart signal in 76.2% of the 500 analyzed cells (Fig. 3). The MLL-MLLT1 gene rearrangement was confirmed by multiplex RT-PCR using the HemaVision kit (DNA Technology, Research Park, Aarhus, Denmark). However, 2 different amplicons (319 bp and 432 bp) were observed, and we identified the 2 amplicons by DNA sequencing. Both amplicons contained a t(11;19) (q23;p13.3)(MLL; MLLT1) translocation (Fig. 4). The patient underwent induction chemotherapy with Hyper-CVAD from March 2010. Complete remission was noted on the follow-up bone marrow study, and no MLL gene rearrangement was observed on follow-up FISH analysis. Subsequently, she underwent consolidation chemotherapy until June 2010; however, she died because of brain ischemia in the pons and the region of the middle cerebral artery.


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 - Korean J Lab Med (2011)

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).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3111038&req=5

Figure 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).
Mentions: A 40-yr-old woman underwent breast surgery for cancer of the right breast and received 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) and radiation therapy (dose, 5,900 cGy), followed by anticancer endocrine therapy with tamoxifen. Complete blood cell counts obtained at 15 months after chemotherapy indicated acute leukemia: white blood cell count, 3.5 × 109/L with 15% blasts; Hb level, 5.8 g/dL; and platelet count, 31.0 × 109/L. Bone marrow examination showed hypercellular marrow with increased blasts, accounting for up to 95% of all bone marrow nucleated cells (Fig. 1). An immunophenotyping study using flow cytometry revealed that the blasts were positive for CD19, CD34, and cytoplasmic CD79a and negative for CD2, CD3, CD5, CD7, CD10, CD13, CD14, CD20, CD22, CD33, CD41, CD117, and myeloperoxidase. On the basis of the immunophenotype of the blasts, we diagnosed the patient with B-ALL. Cytogenetic analysis of the bone marrow aspirates by using the G-banding revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16] (Fig. 2). FISH performed using LSI MLL dual color, break apart rearrangement probes (Abbott Molecular, Des Plaines, IL, USA) showed an MLL break apart signal in 76.2% of the 500 analyzed cells (Fig. 3). The MLL-MLLT1 gene rearrangement was confirmed by multiplex RT-PCR using the HemaVision kit (DNA Technology, Research Park, Aarhus, Denmark). However, 2 different amplicons (319 bp and 432 bp) were observed, and we identified the 2 amplicons by DNA sequencing. Both amplicons contained a t(11;19) (q23;p13.3)(MLL; MLLT1) translocation (Fig. 4). The patient underwent induction chemotherapy with Hyper-CVAD from March 2010. Complete remission was noted on the follow-up bone marrow study, and no MLL gene rearrangement was observed on follow-up FISH analysis. Subsequently, she underwent consolidation chemotherapy until June 2010; however, she died because of brain ischemia in the pons and the region of the middle cerebral artery.

Bottom Line: The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.

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.

Show MeSH
Related in: MedlinePlus