Auto-Ubiquitination-Induced Degradation of MALT1-API2 Prevents BCL10 Destabilization in t(11;18)(q21;q21)-Positive MALT Lymphoma

BACKGROUND: The translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration associated with MALT lymphoma and results in constitutive NF-kappaB activity via the expression of an API2-MALT1 fusion protein. The properties of the reciprocal MALT1-API2 were never investigated as it was reported to be rarely transcribed. PRINCIPAL FINDINGS: Our data indicate the presence of MALT1-API2 transcripts in the majority of t(11;18)(q21;q21)-positive MALT lymphomas. Based on the breakpoints in the MALT1 and API2 gene, the MALT1-API2 protein contains the death domain and one or both immunoglobulin-like domains of MALT1 (approximately 90% of cases)--mediating the possible interaction with BCL10--fused to the RING domain of API2. Here we show that this RING domain enables MALT1-API2 to function as an E3 ubiquitin ligase for BCL10, inducing its ubiquitination and proteasomal degradation in vitro. Expression of MALT1-API2 transcripts in t(11;18)(q21;q21)-positive MALT lymphomas was however not associated with a reduction of BCL10 protein levels. CONCLUSION: As we observed MALT1-API2 to be an efficient target of its own E3 ubiquitin ligase activity, our data suggest that this inherent instability of MALT1-API2 prevents its accumulation and renders a potential effect on MALT lymphoma development via destabilization of BCL10 unlikely

Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32)

The BCR-ABL1 fusion kinase is frequently associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia but is rare in T-cell acute lymphoblastic leukemia (T-ALL). We recently identified NUP214-ABL1 as a variant ABL1 fusion gene in 6% of T-ALL patients. Here we describe the identification of another ABL1 fusion, EML1-ABL1, in a T-ALL patient with a cryptic t(9;14)(q34;q32) associated with deletion of CDKN2A (p16) and expression of TLX1 (HOX11). Echinoderm microtubule-associated protein-like 1-Abelson 1 (EML1-ABL1) is a constitutively phosphorylated tyrosine kinase that transforms Ba/F3 cells to growth factor-independent growth through activation of survival and proliferation pathways, including extracellular signal-related kinase 1/2 (Erk1/2), signal transducers and activators of transcription 5 (Stat5), and Lyn kinase. Deletion of the coiled-coil domain of EML1 abrogated the transforming properties of the fusion kinase. EML1-ABL1 and breakpoint cluster region (BCR)-ABL1 were equally sensitive to the tyrosine kinase inhibitor imatinib. These data further demonstrate the involvement of ABL1 fusions in the pathogenesis of T-ALL and identify EML1-ABL1 as a novel therapeutic target of imatinib

Transitional Flow in a Rushton Turbine Stirred Tank

The authors gratefully acknowledge the financial support from the National Natural Science Foundation of ChinaPeer reviewedPostprin

Prepn. of adsorbent for alpha-amylase - by crosslinking starch grains and comminuting grains or treating with enzyme

In prepn. of an adsorbent for alpha-amylase by cross-linking starch grains, before or during gelatinisation, using a known cross-linking agent, the cross-linked starch prod. is comminuted and/or enzymatically activated. The comminution is pref. by grinding, to a factor of 1-100. Activation is with at least 0.25 (2-12.5) units of alpha-amylase w.r.t. 1 mg of starch, for an incubation time of at least 0.5 (1-3) days at -20 to 30 (2-10) deg. C, and partic. in a buffer at pH 4-12. The powdered treated prod. is granulated with a gelling agent, pref. an aq. alginate soln., followed opt. by treatment with a salt soln., esp. an aq. soln. of a Ca salt. Esp., a suspension of the powdered starch prod. in a 0.1-2.5 wt./vol. alginate soln. in distilled water is treated dropwise with an aq. soln. of a Ca salt, esp. an at least 0.1M soln. of CaCl2, to form the Ca(2+) alginate complex. The powdery starch prod. may be used as a 5-30 wt./vol. aq. suspension