Therapy-related Myeloid Leukaemia in Patients Treated for Breast Cancer

Siobhan Battersby, Praveen Sharma, Dorothy Hung, Luke St Heaps, Dale Wright

Sydney Genome Diagnostics, Children’s Hospital at Westmead, NSW, Australia

Background:

The recurrent t(8;21) abnormality found in primary acute myeloid leukaemia (AML) is associated with a favourable prognosis. In therapy-related myeloid leukaemia (t-AML), previous exposure to topoisomerase-II inhibitors tends to be associated with secondary abnormalities involving balanced rearrangements at 11q23 (KMT2A) and 21q22 (RUNX1). Breast cancer is often treated with topoisomerase-II inhibitors and t-AML can be associated with secondary acquired abnormalities.

Aim: We present two cases identified with t(8;21) following cytotoxic therapy for breast cancer.

Method:

Case 1: 51yo female with pancytopenia and blasts on peripheral blood. The patient was 2 years post chemotherapy for breast cancer.

Case 2: 61yo female with blasts on peripheral blood and previously diagnosed with breast cancer.

These patients were investigated by karyotyping of 24hr and 48hr synchronised cultures, initiated and harvested according to standard laboratory protocols. Twenty G-band cells were analysed. FISH was performed using the t(8;21) probe for RUNX1/RUNX1T1 (VYSIS).

Results:

Case 1 showed a karyotype involving 45,X,-X,t(8;21)(q22;q22,del(9)(q22q32)[15]/46,XX[5]. FISH results failed. Case 2 showed a more complex karyotype involving 46,XX,t(8;17;21)(q22;q23;q22),t(10;20)(p15;p11.2)[14]/46,XX[6]. FISH results showed gene fusion of RUNX1/RUNX1T1 probe.

Conclusion:

The finding of the t(8;21) and variant t(8;17;21) with RUNX1/RUNX1T1 gene fusion is consistent with a secondary abnormality associated with t-AML following breast cancer treatment. Although the t(8;21) has a favourable prognosis in primary AML, when found as a secondary abnormality it portends to a more unfavourable outcome.

 


Biography

Hospital Scientist (8th year) currently working in cytogenetics at The Children’s Hospital at Westmead. Completed a Bachelor of Science in 2008 and will be sitting the MHGSA exam in March this year.

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