MicroRNAs are small non-coding RNAs that act at the post-transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. Because of their discovery, microRNAs have been associated with almost every normal cell function, including proliferation, differentiation and apoptosis. Several lines of evidence suggest that they have an important role in normal hematopoiesis as exemplified by the role of mir-155 and mir-150 in the differentiation of B and T lymphocytes, the suppressive role of mir-221 and mir-222 in erythroid differentiation, the inhibitory effect of mir-181 on hematopoietic differentiation and the induction of myeloid differentiation by mir-223. Moreover, they play a role both as oncogenes, probably by a variety of mechanisms, namely through elimination of tumor suppressor proteins, or as tumor suppressor genes by targeting oncogenic mRNAs. Their aberrant expression has been associated with solid tumors and hematopoietic malignancies as suggested by the frequent deletion of mir-15a and mir-16-1 in chronic lymphocytic leukemia, the increased levels of mir-155 in diffuse large B-cell lymphomas and the increased levels of mir-181 in acute myeloid leukemia M1 and M2. The purpose of this review is to summarize current knowledge on the role of microRNAs in normal hematopoiesis and hematopoietic malignancies and, moreover, to highlight their role as potential therapeutic tools.

The thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS) is a rare disorder characterized by microangiopathic hemolysis and thrombocytopenia. We have undertaken a retrospective analysis of the clinical characteristics, treatment outcome, and prognosis of 48 patients diagnosed and treated in our institution during a 13-year period. Among our patients 22 (46%) had fever, 35 (73%) neurological abnormalities, and 22 (46%) renal impairment at presentation of the syndrome. All patients were treated with a multimodality regimen including plasma exchange, steroids, antiplatelet agents, and IgG infusion. Of the 48 patients, 41 achieved complete remission, two had a partial response, and five had no response and died of progressive disease. Within a median follow-up period of 40 months, ten of the 41 patients who had achieved remission relapsed, most of them within the first 2 years, and nine of these responded promptly to plasma exchange therapy. Eight deaths were observed, seven of refractory disease and one in fourth relapse. The analysis of prognostic factors revealed advanced age and severe renal impairment (creatinine levels above 2 mg%) as the only parameters associated with treatment failure and poor outcome. However, none of the pretreatment characteristics proved to be of prognostic value regarding the probability of relapse. In conclusion, TTP/HUS represent a syndrome of variable clinical expression and aggressiveness. The use of a multimodality regimen in our series produced a high response rate. Nevertheless, the early identification, based on clinical characteristics, of poor-prognosis cases that probably need more or alternative forms of treatment is an issue that remains to be elucidated in prospective trials.

In order to assess the diagnostic value of procalcitonin, 158 patients with febrile neutropenia from centres across Europe were studied. Patients with fever were diagnosed on the basis of either: (1) clinical, radiological and microbiological criteria; or (2) the procalcitonin value. In the latter case, concentrations of 0.5-1.0 ng/mL were considered diagnostic of localised infection, concentrations of 1.0-5.0 ng/mL of bacteraemia, and concentrations of > 5.0 ng/mL of severe sepsis. Procalcitonin and C-reactive protein were estimated daily in serum by immunochemiluminescence and nephelometry, respectively. Overall, the sensitivity (specificity) of procalcitonin for bacteraemia was 44.2% (64.3%) at concentrations of 1.0-5.0 ng/mL, and 83.3% (100%) for severe sepsis at concentrations of > 5.0 ng/mL. It was concluded that procalcitonin is a marker strongly suggestive of severe sepsis at concentrations of > 5.0 ng/mL. Estimated concentrations of < 0.5 ng/mL indicate that infection is unlikely, but it was observed that bacteraemia associated with coagulase-negative staphylococci may fail to elevate serum procalcitonin levels.

Among 387 cases of non-Hodgkin’s lymphoma (NHL) treated in our units between January 1977 and December 1990, 52 (13.4%) had primary extranodal (PE) NHL of the head and neck. The median age was 55 years with a M:F ratio of 1.9:1. The most frequent primary site was the tonsil (28 cases), followed by oral cavity, parotid gland, orbit and other sites. The aggressive histological subtypes predominate. 55.2% of the patients were in stage I and 44.8% in stage II of disease. The CR rate was high (94.2%). The 5 years’ overall survival rate was 65% and it was influenced mainly by stage (stage I 82.5% vs. 48.7% in stage II). Sex, age and histology did not significantly affect survival rate. Patients with primary Waldeyer’s ring involvement (WR group) did not differ significantly from the other primary sites analyzed as a group (non-WR group) in respect to median age, sex distribution, histology and CR rates. They differed, however, in: (1) stage distribution with stage II disease more frequent in the WR group; (2) overall survival and disease-free survival both of which were significantly better in the non-WR group; and (3) the high incidence of GI tract involvement as initial manifestation of relapse in the WR group. It is concluded that the behaviour of the Waldeyer’s ring PE-NHL is rather distinctive and should be considered separately from the other PE-NHL of the head and neck.