M Rocco

A novel crosstalk between calcium/calmodulin kinases II and IV regulates cell proliferation in myeloid leukemia cells

CaMKs link transient increases in intracellular Ca(2+) with biological processes. In myeloid leukemia cells, CaMKII, activated by the bcr-abl oncogene, promotes cell proliferation. Inhibition of CaMKII activity restricts cell proliferation, and correlates with growth arrest and differentiation. The mechanism by which the inhibition of CaMKII results in growth arrest and differentiation in myeloid leukemia cells is still unknown. We report that inhibition of CaMKII activity results in an upregulation of CaMKIV mRNA and protein in leukemia cell lines. Conversely, expression of CaMKIV inhibits autophosphorylation and activation of CaMKII, and elicits G0/G1cell cycle arrest,impairing cell proliferation. Furthermore, U937 cells expressing CaMKIV show elevated levels of Cdk inhibitors p27(kip1) and p16(ink4a) and reduced levels of cyclins A, B1 and D1. These findings were also confirmed in the K562 leukemic cell line. The relationship between CaMKII and CaMKIV is also observed in primary acute myeloid leukemia (AML) cells, and it correlates with their immunophenotypic profile. Indeed, immature MO/M1 AML showed increased CaMKIV expression and decreased pCaMKII, whereas highly differentiated M4/M5 AML showed decreased CaMKIV expression and increased pCaMKII levels. Our data reveal a novel cross-talk between CaMKII and CaMKIV and suggest that CaMKII suppresses the expression of CaMKIV to promote leukemia cell proliferation.

Lymph Node Fine-Needle Cytology of Non-Hodgkin Lymphoma: Diagnosis and Classification by Flow Cytometry

In the last decades, lymph node fine-needle cytology (FNC), coupled with flow cytometry (FC), has gained a role in the diagnosis and classification of non-Hodgkin lymphoma (NHL). The combination of FNC/FC allows the diagnosis and classification of NHL in lymph node samples with a high sensitivity and specificity by combining cytological features and specific phenotypic profiles. The present review provides a brief technical description of FC and a detailed analysis of the current markers and their combinations (diagnostic algorithm) for the diagnosis and classification of NHL. The basic principles of clonality assessment, as well as the diagnostic strengths and weaknesses of the procedure, are reported. The current diagnostic algorithms for NHL classification are critically reviewed with a focus on specific problems related to single entities. Moreover, this review provides a detailed analysis of the different clinical contexts in which FNC/FC is performed and related implications. Future and further applications of FNC/FC for NHL are also discussed.