Although deregulated expression of specific microRNAs (miRNAs) has been described in solid cancers and leukemias, little evidence of miRNA deregulation has been reported in ALK-positive (ALK ؉ ) anaplastic large cell lymphomas (ALCL). These tumors overexpress the major antiapoptotic protein myeloid cell leukemia 1 (MCL-1), a situation that could compensate for the lack of BCL-2. We report that ALK ؉ ALCL cell lines and biopsy specimens (n ‫؍‬ 20) express a low level of miR-29a and that this down- IntroductionAnaplastic lymphoma kinase-positive (ALK ϩ ) anaplastic large cell lymphoma (ALCL) is now recognized as a distinct entity in the World Health Organization (WHO) classification of hematopoietic tumors 1,2 and is characterized by the expression of an oncogenic fusion protein involving the ALK tyrosine kinase receptor. 3,4 Most of the activated pathways downstream to this fusion protein with a constitutive tyrosine kinase activity have been characterized and play major roles in lymphomagenesis in ALK ϩ ALCL, controlling key cellular processes such as proliferation, survival, and cell migration (for review see Chiarle et al 5 ). Another characteristic of ALK ϩ ALCLs is the lack or low expression of the antiapoptotic proteins BCL-2 and BCL-XL, suggesting a possible explanation for their relatively good prognosis. However, these tumors overexpressed MCL-1 (myeloid cell leukemia-1), an oncogene of particular interest, belonging to BCL-2 family of apoptosisregulating proteins, 6 and also involved in programming differentiation 7 and promoting cell viability. 8 MCL-1 expression could compensate for the lack of immunohistochemically detectable BCL-2 and BCL-XL expression in ALK ϩ ALCL. [9][10][11] Some studies have suggested that the Jak-STAT and PI3K pathways activated in ALK ϩ tumors could be involved in up-regulating MCL-1 but other pathways at the posttranscriptional level, such as microRNAs, might also contribute to its high expression in ALK ϩ ALCL cases (see reviews by Akgul 12 and Michels et al 13 ).Micro-RNAs (miRNAs) are small noncoding RNAs that regulate target gene expression posttranscriptionally through base pairing within the 3Ј-UTR regions of the target messenger RNAs and inducing their degradation, translational inhibition, or both of the encoded proteins. 14,15 MiRNAs play key regulator roles in fundamental biologic processes including cell differentiation, apoptosis, cell proliferation, organ development, and hematopoiesis (see review by Kluiver et al 16 ). family members have been shown to be down-regulated in several hematopoietic neoplasms, including chronic lymphocytic leukemia with poor prognosis, 17 acute myeloid leukemia, 18 and mantle cell lymphoma, 19 as well as solid cancers such as lung cancer, 20 hepatocellular carcinoma, 21 and invasive breast cancer. 22 More particularly, miR-29a, miR-29b, or both directly target the antiapoptotic protein MCL-1 in cholangiocarcinoma, 23 hepatocellular carcinoma, 21 and acute myeloid leukemia (AML). 18 However, to date, only one study has addressed th...

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