Rabbit Anti-PAX5 monoclonal antibody, clone KK19-98

PurposeSomatic deletions that affect the lymphoid transcription factor-coding gene IKZF1 have previously been reported as independently associated with a poor prognosis in pediatric B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). We have now refined the prognostic strength of IKZF1 deletions by analyzing the effect of co-occurring deletions.Patients and MethodsThe analysis involved 991 patients with BCP ALL treated in the Associazione Italiana Ematologia ed Oncologia Pediatrica-Berlin-Frankfurt-Muenster (AIEOP-BFM) ALL 2000 trial with complete information for copy number alterations of IKZF1, PAX5, ETV6, RB1, BTG1, EBF1, CDKN2A, CDKN2B, Xp22.33/Yp11.31 (PAR1 region; CRLF2, CSF2RA, and IL3RA), and ERG; replication of findings involved 417 patients from the same trial.ResultsIKZF1 deletions that co-occurred with deletions in CDKN2A, CDKN2B, PAX5, or PAR1 in the absence of ERG deletion conferred the worst outcome and, consequently, were grouped as IKZF1(plus). The IKZF1(plus) group comprised 6% of patients with BCP ALL, with a 5-year event-free survival of 53 6% compared with 79 +/- 5% in patients with IKZF1 deletion who did not fulfill the IKZF1(plus) definition and 87 +/- 1% in patients who lacked an IKZF1 deletion (P .001). Respective 5-year cumulative relapse incidence rates were 44 +/- 6%, 11 +/- 4%, and 10 +/- 1% (P .001). Results were confirmed in the replication cohort, and multivariable analyses demonstrated independence of IKZF1(plus). The IKZF1(plus) prognostic effect differed dramatically in analyses stratified by minimal residual disease (MRD) levels after induction treatment: 5-year event-free survival for MRD standard-risk IKZF1(plus) patients was 94 +/- 5% versus 40 +/- 10% in MRD intermediate- and 30 +/- 14% in high-risk IKZF1(plus) patients (P .001). Corresponding 5-year cumulative incidence of relapse rates were 6 +/- 6%, 60 +/- 10%, and 60 +/- 17% (P .001).ConclusionIKZF1(plus) describes a new MRD-dependent very-poor prognostic profile in BCP ALL. Because current AIEOP-BFM treatment is largely ineffective for MRD-positive IKZF1(plus) patients, new experimental treatment approaches will be evaluated in our upcoming trial AIEOP-BFM ALL 2017. (c) 2018 by American Society of Clinical Oncology

A 5-y-old female Golden Retriever was presented with a 2-wk history of hyporexia, vomiting, diarrhea, lethargy, weight loss, polyuria, and polydipsia. Clinical examination and ultrasonography revealed multiple organ enlargement with gallbladder and kidney nodules suggestive of disseminated neoplasia. Hematologic and biochemical analyses revealed pancytopenia, hypercalcemia, and monoclonal IgA gammopathy suspicious for a plasma cell neoplasm. Bone marrow and blood smear examination revealed neoplastic atypical cells highly suggestive of lymphoid origin. Autopsy confirmed the presence of homogeneous white masses and multifocal pale infiltrates in the spleen, kidney, small intestine, gallbladder, and urinary tract. Histologic features were consistent with a multicentric atypical plasma cell tumor. Tumor cells were negative for CD204, IBA-1, E-cadherin, CD3, CD5, CD79a, CD20, and PAX5, and positive for MUM1, consistent with plasma cell origin. The presence of > 20% of circulating blastic plasma cells was consistent with primary plasma cell leukemia with plasmablastic morphology, a disease rarely described in veterinary medicine.