Diagnosis of minimal residual disease in bone marrow and blood in cancer patients - Methods and clinical implications

For some types of cancer the presence of tumour cells in the bone marrow at diagnosis is an independent prognostic factor. Immunocytochemical staining techniques have led to improvements in the ability to detect occult cancer cells in bone marrow. One major limitation of these methods is that the monoclonal antibodies used are only tumour-associated and not tumour-specific. Therefore, some cross reaction with normal cells can occur. Polymerase chain reaction (PCR) has been applied extensively to measure minimal residual disease in bone marrow and blood of lymphomas carrying the t(14;18) translocation and Philadelphia chromosome (PH)-positive chronic myelogenous leukaemia One major limitation of the PCR method is that not all tumours of interest carry chromosomal translocation. Reverse transcription PCR assays (RT-PCR) that screen for expression of tissue-specific and tumour-associated genes mRNA in bone marrow and blood have been developed. As in the case of immunocytochemistry, not all RT-PCR assays have the specificity required for them to be used safely in the clinic. Therefore, prior to introducing these methods in the clinic, standardized protocols need to be developed and validated.