Korean J Lab Med.  2010 Jun;30(3):255-259. 10.3343/kjlm.2010.30.3.255.

A Case of Therapy-related ALL with MLL Gene Rearrangement Following Treatment of Breast Cancer

• Cho J
• Hur M
• Moon HW
• Yun YM
• Lee CH
• Lee HG

• KMID: 1781624
• DOI: http://doi.org/10.3343/kjlm.2010.30.3.255

Abstract

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1x10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0x10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

Keyword

Therapy; ALL; Topoisomerase II inhibitor; MLL gene rearrangement

MeSH Terms

Antibiotics, Antineoplastic/therapeutic use
Blood Cell Count
Bone Marrow/pathology
Breast Neoplasms/*drug therapy/radiotherapy
Chemotherapy, Adjuvant
Combined Modality Therapy
Cyclophosphamide/therapeutic use
Cytogenetic Analysis
Epirubicin/therapeutic use
Female
Fluorouracil/therapeutic use
Gene Rearrangement
Hematopoietic Stem Cell Transplantation
Humans
In Situ Hybridization, Fluorescence
Myeloid-Lymphoid Leukemia Protein/*genetics
Precursor Cell Lymphoblastic Leukemia-Lymphoma/*etiology/genetics/pathology
*Translocation, Genetic

Figure

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  Fig. 1. Bone marrow aspirate smear showing lymphoblasts (Wright's stain, ×1,000).

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  Fig. 2. FISH analysis showing MLL gene rearrangement with separate red and green signals (performed using LSI MLL dual-color, break-apart rearrangement probe, Vysis, USA; ×1,000).

Reference

1.Leone G., Mele L., Pulsoni A., Equitani F., Pagano L. The incidence of secondary leukemias. Haematologica. 1999. 84:937–45.

2.Pedersen-Bjergaard J., Andersen MK., Christiansen DH., Nerlov C. Genetic pathways in therapy-related myelodysplasia and AML. Blood. 2002. 99:1909–12.

3.Pagano L., Pulsoni A., Mele L., Leone G. Clinical and epidemiological features of ALL following a previous malignancy. Leuk Lymphoma. 2000. 39:465–75.

4.Andersen MK., Christiansen DH., Jensen BA., Ernst P., Hauge G., Pedersen-Bjergaard J. Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on two new cases and review of the literature since 1992. Br J Haematol. 2001. 114:539–43.

5.Pagano L., Pulsoni A., Tosti ME., Annino L., Mele A., Camera A, et al. Acute lymphoblastic leukaemia occurring as second malignancy: report of the GIMEMA archive of adult acute leukaemia. Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto. Br J Haematol. 1999. 106:1037–40.

6.Song SH., Bin JS., Kim JH., Park YS., Park KC., Shun DJ, et al. Therapy-related acute myelogenous leukemia with complex chromosomal defect. Korean J Hematol. 1992. 27:117–22.

7.Hur M., Lee DS., Shin HY., Ahn HS., Kim BK., Cho HI. Four cases of therapy-related leukemia. J Korean Med Sci. 1999. 14:327–9.

8.Kim M., Lim J., Kim Y., Han K., Kang CS., Kim HJ, et al. A case of therapy-related AML associated with inv(16), with subsequent development of t(9;22). Leukemia. 2006. 20:746–8.

9.Lee SY., Kim M., Lim J., Kim Y., Han K., Kim SY, et al. A case of therapy-related AML associated with inv(16). Korean J Lab Med. 2007. 27:19–21.

10.Lee SG., Choi JR., Kim JS., Park TS., Lee KA., Song J. Therapy-related ALL with t(9;22)(q34;q11.2):a case study and review of the literature. Cancer Genet Cytogenet. 2009. 191:51–4.

11.Smith SM., Le Beau MM., Huo D., Karrison T., Sobecks RM., Anastasi J, et al. Clinical-cytogenetic associations in 306 patients with therapy-related myelodysplasia and myeloid leukemia: the University of Chicago series. Blood. 2003. 102:43–52.

12.Secker-Walker LM., Moorman AV., Bain BJ., Mehta AB. Secondary acute leukemia and myelodysplastic syndrome with 11q23 abnormalities. EU Concerted Action 11q23 Workshop. Leukemia. 1998. 12:840–4.

13.Ishizawa S., Slovak ML., Popplewell L., Bedell V., Wrede JE., Carter NH, et al. High frequency of pro-B ALL in adults with secondary leukemia with 11q23 abnormalities. Leukemia. 2003. 17:1091–5.

14.Tsujioka T., Wada H., Yamamori S., Otsuki T., Suemori S., Kondo T, et al. MLL/AF-1p fusion in therapy-related early pre-B ALL with t(1;11)(p32;q23) translocation developing in the relapse phase of acute promyelocytic leukemia. Int J Hematol. 2003. 78:439–42.

15.Millot F., Brizard F., Sorel N., Preudhomme C., Cividin M., Guilhot F, et al. Therapy-related ALL with MLL rearrangement following treatment of Burkitt's leukemia. Leuk Lymphoma. 2005. 46:925–7.

16.Hrusak O., Porwit-MacDonald A. Antigen expression patterns reflecting genotype of acute leukemias. Leukemia. 2002. 16:1233–58.

17.Schoch C., Kern W., Schnittger S., Hiddemann W., Haferlach T. Karyotype is an independent prognostic parameter in therapy-related AML (t-AML): an analysis of 93 patients with t-AML in comparison to 1091 patients with de novo AML. Leukemia. 2004. 18:120–5.

18.Pagano L., Pulsoni A., Tosti ME., Mele A., Mele L., Corvatta L, et al. Acute leukemia following a previous malignancy: do acute lymphoid leukemia and AML have common risk factors? Hematol J. 2000. 1:329–32.