Title: Pseudo Pelger-Huët anomaly in myelodysplastic syndrome: hyposegmented or apoptotic neutrophil?
Abstract: prognostic feature in MDS that is associated with an imminent risk for leukemic transformation.We do not, however, base a diagnosis of ALIP on bone marrow clot sections alone.All myeloblast clusters identified in marrow clot sections were confirmed by trephine biopsy prior to immunohistochemical staining.Our use of bone marrow clot sections to examine VEGF and receptor expression was predicated on the superior staining characteristics of bone marrow clot sections as compared to cores under the conditions used for staining in this study.Nevertheless, Mangi's letter now prompts us to include a figure showing VEGF expression in ALIP in a bone marrow trephine biopsy.Although the level of staining is not as optimal as that observed in the clot sections provided in the original manuscript, VEGF expression is clearly demonstrated (Figure 1).Dr Mangi incorrectly states that we conclude that the VEGF/ receptor profile is specific to ALIP.We do not state that the observed staining characteristics are specific to ALIP and, indeed, a similar pattern is observed in AML, an observation that we report from our own data in the manuscript.But acquisition of the VEGF autocrine responsive phenotype may represent an early event in AML evolution that might also facilitate homotypic myeloblast adhesion.Although we report the characteristic staining pattern for VEGF/receptor in isolated myelomonocytic precursors in 8 of 8 patients with refractory anemia, we do not describe ALIP in this low-risk FAB category, as stated by Dr Mangi.We fully agree with Dr Mangi that the International Prognostic Scoring System (IPSS) in MDS is a useful scoring system based upon clinical and pathologic features at disease presentation. 4 Our series of patients was not restricted to bone marrow specimens obtained at diagnosis and includes patients with proliferative chronic myelomonocytic leukemia (CMML), which are excluded from the IPSS.An important aspect of our study overlooked by Dr Mangi is that, while we and others have demonstrated the expression of VEGF in hematopoietic malignancies, [5][6][7][8] this is one of the first reports to characterize the functional relevance as it relates to potential autocrine stimulation of tumor growth and survival.Such translational investigations are critical to the development of novel therapies targeting the VEGF-receptor axis and to thereby offer the potential to impact leukemia progenitor growth and development.