A case of therapy-related acute lymphoblastic leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 gene rearrangement.
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.
Department of Laboratory Medicine, Korea University College of Medicine, Seoul, Korea.
Byong-Joon
BJ
Yoo
Myung-Hyun
MH
Nam
Hwa-Jung
HJ
Sung
Chae-Seung
CS
Lim
Chang-Kyu
CK
Lee
Yun-Jung
YJ
Cho
Kap-No
KN
Lee
Soo-Young
SY
Yoon
D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001483:Base Sequence; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D002880:Chromosomes, Human, Pair 11; D002888:Chromosomes, Human, Pair 19; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D015321:Gene Rearrangement; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D016130:Immunophenotyping; D007621:Karyotyping; D008969:Molecular Sequence Data; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000175:diagnosis* / Q000235:genetics; D017422:Sequence Analysis, DNA; D013629:Tamoxifen / Q000627:therapeutic use; D014157:Transcription Factors / Q000235:genetics*; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; C497422:KMT2A protein, human; C081448:MLLT1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D013629:Tamoxifen; D051788:Myeloid-Lymphoid Leukemia Protein; D004317:Doxorubicin; D003520:Cyclophosphamide; D011495:Histone-Lysine N-Methyltransferase
Leukemia. 1991 Dec;5(12):1064-8
1774955
Leukemia. 2003 Apr;17(4):700-6
12682627
Am J Clin Pathol. 2010 Jan;133(1):75-82
20023261
Leukemia. 2002 Jul;16(7):1233-58
12094248
Blood. 1994 Jul 15;84(2):570-3
8025282
Leukemia. 2003 Jun;17(6):1091-5
12764373
Am J Clin Pathol. 2007 Jan;127(1):24-30
17145626
Blood. 1993 Nov 15;82(10):3220-1
8219210
J Clin Oncol. 1999 Jan;17(1):191-6
10458233
Leuk Lymphoma. 2000 Nov;39(5-6):465-75
11342330
Leukemia. 1998 May;12(5):805-10
9593285
Am J Hematol. 1989 Aug;31(4):253-7
2741924
Leukemia. 1993 Feb;7(2):152-60
8426468
Br J Haematol. 2001 Sep;114(3):539-43
11552977
Leukemia. 1999 Dec;13(12):2116-8
10602439
Korean J Lab Med. 2010 Jun;30(3):255-9
20603585
J Clin Oncol. 1994 May;12(5):909-15
8164041
Br J Haematol. 1996 Mar;92(3):673-80
8616034
Blood. 2003 Oct 1;102(7):2395-402
12805060
Blood. 2009 Apr 23;113(17):4011-5
19144982
Leukemia. 1998 May;12(5):840-4
9593290