Journal List > Korean J Lab Med > v.30(3) > 1011640

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

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.

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Fig. 1.
Bone marrow aspirate smear showing lymphoblasts (Wright's stain, ×1,000).
kjlm-30-255f1.tif
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).
kjlm-30-255f2.tif
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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