Tumor-Specific S-Phase Fractions of B-Cell Acute Lymphoblastic Leukemias Are Significantly Higher in the Bone Marrow Than in Peripheral Blood.
Matthew R Simmons, Nicholas A Lancia, Paisarn Boonsakan, Samer Z Al-Quran, Raul C Braylan, Ying Li. University of Florida, Gainesville
Background: B-cell Acute lymphoblastic leukemia (B-ALL) can be diagnosed in peripheral blood (PB) or bone marrow (BM) samples, often by flow cytometry (FCM). FCM is also used to assess DNA ploidy and cell cycle kinetics, including proliferation, i.e. S-Phase Fraction (SPF). While some studies have suggested prognostic differences based on tumor-specific SPF, its significance in B-ALL remains less clear because of varied results in different studies. In our clinical practice, we have noticed that the SPF of tumor cells in PB is much lower than that in the BM, even within the same patient. We used B-ALL as a model to test the hypothesis that the tumor-specific SPFs in the BM are on average higher than that in the PB.
Design: We identified cases diagnosed as B-ALL in our flow cytometry laboratory between 1999 and 2008 that also had DNA analysis by FCM including measurement of SPF. We selected thirty cases each of B-ALL in PB and BM. DNA analysis and SPF measurements were performed by FCM in each case using either DRAQ5 or propidium iodide (Cycle test). When both a PB and BM sample were available for the same patient, the same method was used for DNA analysis and to measure SPF. The results from the PB/BM samples were then compared using the Mann-Whitney test.
Results: The mean age of the study population was 19 years, with a range of 3 months to 79 years, with a childhood/adult ALL ratio of 2:3. The SPF values in the BM group (mean 14.2%) were significantly higher than those in the PB group (mean 3.8%, p<0.001), as depicted in the figure below.
Conclusions: The tumor-specific SPFs of B-ALL in the BM are significantly higher than those in PB, a finding that may be utilized for treatment purposes. The results of our study indicate the circulating blasts in PB have different cell cycle kinetics. It is possible that our observations may represent a general phenomenon that any tumor cells circulating in PB have a relatively lower SPF. The reason for the varied SPF results from previous studies may be due to different diagnostic samples. While the diagnosis of ALL can often be made in either PB or BM sample, any future studies examining the prognostic significance of SPF in ALL will need to control for sample type.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 161, Wednesday Morning