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

Jinhee Cho; Mina Hur; Hee Won Moon; Yeo-Min Yun; Chang Hoon Lee; Hong Ghi Lee

doi:10.3343/kjlm.2010.30.3.255

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Cho, Hur, Moon, Yun, Lee, and Lee: A Case of Therapy-related ALL with MLL Gene Rearrangement Following Treatment of Breast Cancer

Case Report

Korean J Leg Med 2010;30(3):255-259.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.3.255

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

Jinhee Cho, M.D.¹, Mina Hur, M.D.¹, Hee Won Moon, M.D.¹, Yeo-Min Yun, M.D.¹, Chang Hoon Lee, M.D.¹, Hong Ghi Lee, M.D.²

¹Departments of Laboratory Medicine, Seoul, Korea

²Internal Medicine, Konkuk University School of Medicine, Seoul, Korea

Corresponding author: Mina Hur, M.D. Department of Laboratory Medicine, Konkuk University Hospital, Konkuk University School of Medicine, 4-12 Hwayang-dong, Gwangjin-gu, Seoul 143-729, Korea Tel: +82-2-2030-5581, Fax: +82-2-2636-6764 E-mail: dearmina@hanmail.net

Revised 18 January 20105 April 2010 Accepted 3 May 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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, 174.1×10⁹/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0×10⁹/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.

Keywords: Therapy, ALL, Topoisomerase II inhibitor, MLL gene rearrangement

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Fig. 1.

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

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).

Table 1.

Characteristics of the therapy-related ALL cases with 11q23 abnormalities reported since 2001

Cases	Sex/Age	Primary malignancy	Treatment	RT	Secondary malignancy	Latency period (months)	Karyotype	Immunophenotype	Clinical status (months)∗
Andersen et al. (2001) [4]	F/64	Breast cancer	Epirubicin	RT	Pro-B ALL	10	t(4;11)(q21;q23)	CD10^-, CD19⁺, CD22⁺, faint CD34, TdT⁺	PR (NA)
	M/27	Testicular cancer	ETO, CIS, BLO	RT	Pro-B ALL	18	t(4;11)(q21;q23)	CD10, CD19⁺, CD22⁺, faint CD34	CR (NA)
Ishizawa et al. (2003) [13]	F/65	Follicular lymphoma	FLU, MIT, DEXA	ND	Pro-B ALL	13	t(4;11)(q21;q23)	CD10-, CD15^+†, CD65^+†	Alive with disease (2.6)
	M/25	Hodgkin's lymphoma	MOPP/ABV, MIT, THIO, CYP with BMT	RT	Pro-B ALL	96	-X,t(2;15)(q?21;q15),der(11), t(11:?)(q23;?),del(13)(q14q34), etc	CD10-, CD15^+†, CD65^+† CD10-, CD15^+†, CD65^+†	DFS (54) DFS (21)
	F/59	Breast cancer	CYP, DOX, 5-FU	ND	Pro-B ALL	24	t(4;11) (q21;q23),add (5), (q33)
	F/60	Lung cancer	CAB, ETO	RT	Pro-B ALL	NA	t(4;11)(q21;q23)	CD10-, CD15^+†, CD65^+†	Dead (0.4)
	M/69	Lung cancer	NA	NA	Pro-B ALL	NA	MLL rearrangement^‡	CD10-, CD15^+†, CD65^+†	NA
Tsujioka et al. (2003) [14]	M/57	APL with t(15;17)	ATRA, IDA, Ara-C,MIT, DNR, ETO	ND	Pro-B ALL	10	t(1;11)(p32;q23),t(15;17)(q22;q21)	CD10^-, CD19⁺	Dead (10)
Millot et al. (2005) [15]	M/8	Burkitt's lymphoma	CYP, VIC, PD, MTX,DOX, Ara-C, ETO	ND	Pro-B ALL	13	t(4;11)(q21;q23),add(19)(q13)	CD10^-, CD19⁺, CD79a⁺,HLA-DR⁺	CR (NA)
Present case (2010)	F/60	Breast cancer	CYP, EPR, 5-FU	RT	Pro-B ALL	14	t(4;11)(q21;q23)	CD10^-, CD19⁺, CD79a⁺,HLA-DR⁺, CD34⁺, TdT⁺	CR with BMT (10)

^∗ time of follow-up after the diagnosis of therapy-related leukemia;

^† aberrant expression;

^‡ confirmed by FISH

Abbreviations: RT, radiation therapy; F, female; PR, partial remission; NA, not available; M, male; ETO, etoposide; CIS, cisplatin; BLO, bleomycin; CR, complete remission; FLU, fludarabine; MIT, mitoxantrone; DEXA, dexamethasone; ND, not done; MOPP, mustard/vincristine/prednisone/procarbazine ABV, doxorubicin/bleomycin/vinblastine; THIO, thiotepa; CYP, cyclophosphamide; BMT, bone marrow transplantation; DFS, disease-free state; DOX, doxorubicin; 5-FU, 5-fluorouracil; CAB, carboplatin; APL, acute promyelocytic leukemia; ATRA, all-trans retinoic acid; IDA, idarubicin; Ara-C, cytosine arabinoside; DNR, daunorubicin; VIC, vincristine; PD, prednisone; MTX, methotrexate; EPR, epirubicin.

Table 2.

Cases of therapy-related leukemia in Korea

Cases	Sex/Age	Primary malignancy	Treatment	RT	Secondary malignancy	Latency period (months)	Karyotype	Immunophenotype	Clinical status (months)∗
Song et al. (1992) [6]	M/15	Rhabdomyosarcoma	VIC, ACT-D, CYP, AD, CIS	RT	AML, M1	19	-8,+iso7q,del(7)(q32q36),9p+,t(7;20)(p13;q13/1),t(9;11)(q13;q24), etc.	NA	Dead (0.4)
Hur et al. (1999) [7]	F/66	Lung cancer	ETO, IFS, CIS	RT	AML, M2	33	NA	NA	Alive with disease (4)
	M/7	ALL	l-ASP, MTX, DNR	RT	AML, M4	33	NA	NA	Dead (5)
	M/15	NHL	VIC, MTX, DNR, l-ASP, PD	RT	AML, M5b	24	NA	NA	Dead (2)
	F/18	ALL	l-ASP, VIC, MTX, DNR	RT	AML, M2	51	NA	NA	Dead (9)
Kim et al. (2006) [8]	F/43	Follicular lymphoma	FLU, MIT, DEXA	ND	AML, M4 with eosinophilia	10	inv(16)(p14.1q22),+8,t(9;22;14)(q34;q11.2;q22), etc.	CD13⁺, CD33⁺,CD34⁺	CR with BMT (5)^†
Lee et al. (2007) [9]	F/50	Ovarian cancer	CIS, PAT, TPT	ND	AML	43	inv(16)(p13.1q22),+22	CD13⁺, CD14⁺,CD33⁺, CD34⁺,CD64⁺, CD117⁺	Dead (7)
Lee et al. (2009) [10]	F/60	Breast cancer	CMF, EPR, PAT	RT	Pre-B ALL	48	t(9;22)(q34;q11.2),-7	HLA-DR⁺, MPO⁺CD10⁺, CD19⁺,CD79a⁺, TdT⁺,CD13^+‡, CD33^+‡	Follow-up loss after diagnosis

^∗ time of follow-up after the diagnosis of therapy-related leukemia;

^† time of follow-up after BMT;

^‡ aberrant expression.

Abbreviations: RT, radiation therapy; M, male; VIC, vincristine; ACT-D, actinomycin-D; CYP, cyclophosphamide; AD, adriamycin; CIS, cisplatin; NA, not available; F, female; ETO, etoposide; IFS, ifosfamide; L-ASP, L-asparaginase; MTX, methotrexate; DNR, daunorubicin; NHL, non-Hodgkin's lymphoma; PD, prednisone; FLU, fludarabine; MIT, mitoxantrone; DEXA, dexamethasone; ND, not done; CR, complete remission; BMT, bone marrow transplantation; PAT, paclitaxel; TPT, topotecan; CMF, cyclophosphamide/methotrexate/5-fluorouracil; EPR, epirubicin; 5-FU, 5-fluorouracil.

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