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2.
Pathobiology ; 86(2-3): 162-166, 2019.
Article in English | MEDLINE | ID: mdl-30396184

ABSTRACT

BACKGROUND: RUNX1 is a crucial transcription factor for hematological stem cells and well-known for its association with acute lymphoblastic leukemia (ALL) and acute myelogenous leukemia (AML). Besides the translocation t(8; 21) that leads to the RUNX1-RUNX1T1 fusion, somatic mutations of RUNX1 have been discovered. METHODS: Four bone marrow trephine biopsies of patients with CD79a-positive and/or PAX5-positive acute leukemias were investigated by immunohistochemistry (IHC), karyotyping, and next-generation sequencing-based genetic analysis. Data were then compared to a historical collective of AML (n = 42) and 42 cases of AML newly diagnosed at our institution between June 2017 and May 2018. RESULTS: We report on 4 cases of acute leukemia with an equivocal immunophenotype showing expression of CD79a and/or PAX5, which led to a preliminary histopathologic classification as probable ALL/unclassifiable acute leukemia. All cases were positive for CD34 and TdT but negative for several myeloid markers on IHC. Mutational analysis revealed point mutations and indels of RUNX1 and further mutations typical for AML such as TET2, DNMT3A, and SRSF2, and 2 cases had tetrasomy 13 characteristic of RUNX1 mutant AML. CONCLUSION: Aberrant CD79a and/or PAX5 expression can be found in AML cases with RUNX1 mutations even without the translocation t(8; 21). Our series shows the expression of CD79a and PAX5 to be a potential pitfall in the classification of RUNX1 mutant acute leukemia.


Subject(s)
CD79 Antigens/genetics , Core Binding Factor Alpha 2 Subunit/genetics , Leukemia, Myeloid, Acute/genetics , Mutation , PAX5 Transcription Factor/genetics , Adult , Biopsy , Bone Marrow/pathology , DNA Mutational Analysis , Humans , Immunohistochemistry , Immunophenotyping , Karyotyping , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/diagnosis , Sequence Analysis, DNA
3.
Leuk Lymphoma ; 56(3): 608-14, 2015 Mar.
Article in English | MEDLINE | ID: mdl-24884311

ABSTRACT

Current practice in Switzerland for the mobilization of autologous stem cells in patients with myeloma is combining vinorelbine chemotherapy and granulocyte-colony stimulating factor (G-CSF) cytokine stimulation. We prospectively investigated adding intravenous plerixafor to the vinorelbine/G-CSF combination (VGP), and compared it with vinorelbine/plerixafor (VP) and G-CSF/plerixafor (GP) combinations. In a final cohort (VP-late), plerixafor was given on the first day of CD34 + cells increasing to > 15,000/mL peripheral blood. Four consecutive cohorts of 10 patients with myeloma were studied. We observed that intravenously administered plerixafor can be safely combined with vinorelbine/G-CSF. VGP was superior in mobilizing peripheral stem and progenitor cells compared to the three double combinations (VP, GP and VP-late), and GP mobilized better than VP. Our data indicate that the triple combination of VGP is an efficient strategy to collect autologous CD34 + cells, with G-CSF contributing predominantly in this concept. Plerixafor can be safely added to G-CSF and/or vinorelbine chemotherapy.


Subject(s)
Anti-HIV Agents/therapeutic use , Antineoplastic Agents, Phytogenic/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Mobilization/methods , Heterocyclic Compounds/therapeutic use , Multiple Myeloma/drug therapy , Vinblastine/analogs & derivatives , Benzylamines , Cyclams , Drug Synergism , Drug Therapy, Combination/methods , Female , Hematopoietic Stem Cell Transplantation , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Vinblastine/therapeutic use , Vinorelbine
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