B-chronic lymphocytic leukemia (B-CLL) is an indolent lymphoid malignancy with variable prognosis. Adverse prognostic factors comprise treatment resistance, cytogenetics (11q- and 17p-), the presence of unmutated Ig genes, and the more comprehensive activation marker Zap 70. In contrast to diminished sensitivity to chemotherapy, Zap 70+ B-CLL cells retain their responsiveness to manipulation of signal transduction and monoclonals. Xanthohumol (XA) has recently been documented to have an impact on breast cancer cell growth and invasiveness in vitro. Based on these observations, lymphocytes from patients with B-CLL were cultured in the presence of XA in vitro. XA induced a dose-dependent killing of B-CLL cells at an LD(50) ((24 h)) of 24.4 +/- 6.6 microM, independent of known adverse prognostic factors including functional loss of p53. Cell death was associated with poly (ADP)-ribose polymerase cleavage and annexin V positivity, suggestive of an apoptotic mechanism. Surprisingly, p 70(S 6 K) phosphorylation was stimulated upon XA treatment. In conclusion, XA has an antitumor activity on B-CLL cells in vitro. The molecular mechanisms behind this pro-apoptotic effect deserve further investigation.

We demonstrate in this study that routine use of the MFI antigen ratio (CD81/CD58) in addition to the MFC evaluation using WHO classical criteria appears to be an efficient approach to discriminate LB from HG.

Introduction: In recent studies,interleukin-3 receptor alpha chain (IL-3Rα or CD123) has been described as over-expressed on leukemia progenitor/stem cells and low or absent on normal hematopoietic stem cells suggesting that IL-3Rα could represent an important target for the development of new anti-leukemic drugs and a minimal residual disease (MRD) marker. However, CD123 expression on blast cells and its prognostic value in different hematologic malignancies as acute myeloid leukemia (AML), acute lymphoid leukemia (ALL) and refractory anemia with excess blasts (RAEB) are still controversial. In the present study, we retrospectively analyzed the CD123 and other lineage infidelity markers (LIM) expression on blast cells in bone marrow or blood samples from patients with AML, ALL or RAEB and the disease evolution including overall survival of these patients. CD123 was also measured on B-precursors. Methods: Ninety-seven patients suffering from hematologic malignancies including69 AMLs, 21 ALLs (18 B-ALLs and 3 T-ALLs) and 7 RAEBs were retrospectively analyzed in regard to CD123 (clone-FITC 763, BD Pharmingen) and other LIM expression measured by flow cytometry (FCM) on myeloid and lymphoid blasts from 2011 to 2014. CD123 was also analyzed on patients with hematogones (n=23). FCM was performed on 5 and 10-colour flow cytometers with extensive panels to precise leukemia-associated aberrant immunophenotype (LAIP) and blast populations were identified by CD45 vs. side scatter characteristics. The positivity of markers was considered at a threshold of 20%. Results: Among the 97 patients (including 45 deceased, 42 alive and 10 lost in follow-up patients), 54 (55.7%) had a CD123 over-expressed (including 21 deceased, 26 alive and 7 lost in follow-up patients). Forty-five patients with AML (n=69) had a CD123 over-expressed (65.2%). Among these 45 patients, 6 were lost in follow-up and 25 were in refractory/relapse disease or dead. Six patients, including 5/18 B-ALL (27.8%) and 1/3 T-ALL (33.3%), with ALL (n=21) had a CD123 over-expressed (28.6%). Among these 6 patients, 5 were in refractory/relapse disease or dead. Three patients with RAEB (n=7) had a CD123 over-expressed (42.86%). Only over-expressing CD123 patients with RAEB are still alive among the 7 RAEBs. The mean value (+/- SD) of the %CD123 on CD45low in all and in the CD123 positive cases of AML, ALL and RAEB was respectively 35.1 +/- 30.5% and 51.4 +/- 25.5%,18.1+/- 31.1% and 61.2 +/- 27.3% , 29.9 +/- 30.7% and 60.1 +/- 20.5%. CD123 over-expression was not observed on B-precursors. Among the 56 patients undergoing long-term follow-up, 10 shifts (17.9%) and 3 inversed shifts (5.4%) were observed in the CD123 expression. Among all, AML, ALL and RAEB patients, respectively 41 (42.3%), 36 (52.2%), 3 (14.3%) and 2 (28.6%) had LIM with respectively 27 (65.8%), 23 (63.8%), 2 (66.7%) and 2 (100%) patients with CD123 over-expression. Only 14.4%, 18.8%, 4.7% and 0% of respectively all, AML, ALL and RAEB patients demonstrated LIM without CD123 over-expression. Conclusions: Our observations confirm that IL-3Rα is very frequently expressed on leukemia blast cells, in about 2/3 of AMLs and probably in 1/3 of ALLs with a rare loss of expression with antigenic shift of the disease. As expected, CD123 is not expressed on hematogones. CD123 seems actually represent one of the most robust markers to follow MRD with FCM, in AML, ALL and RAEB. No significant association betweenCD123 expression and poor overall survival is clearly observed although CD123 expression seems associated with high relapse rate in ALL. Further prospective investigations are needed to assess the real impact of CD123 expression on disease-free and overall survival. Disclosures No relevant conflicts of interest to declare.

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