ABSTRACT
More than 95% of patients with acute promyelocytic leukemia (APL) are characterized by the reciprocal translocation t(15;17)(q24;21), which involves the promyelocytic leukemia protein (PML) gene on chromosome 15 and the retinoic acid receptor-α (RARA) gene on chromosome 17, leading to the production of the PML::RARA chimeric gene. Additional chromosomal abnormalities are described in all acute myeloid leukemias and occur in approximately one-third of patients with newly diagnosed APL. Here, we report the case of de novo APL showing the classical t(15;17)(q24;q21), a deletion of the short arm of chromosome 6 (6p), and a noncanonical molecular variant of the PML::RARA transcript. Nevertheless, the patient achieved complete remission after treatment with conventional therapy with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Notwithstanding that the molecular pathogenesis of this type of atypical variant still remains unknown, we conclude that this atypical PML::RARA bcr2 fusion gene associated with del(6p) does not seem to alter the effectiveness of combined treatment with ATRA and ATO.
Subject(s)
Leukemia, Promyelocytic, Acute , Humans , Leukemia, Promyelocytic, Acute/diagnosis , Leukemia, Promyelocytic, Acute/drug therapy , Leukemia, Promyelocytic, Acute/genetics , Tretinoin/therapeutic use , Promyelocytic Leukemia Protein/genetics , Oncogene Proteins, Fusion/geneticsABSTRACT
Acute promyelocytic leukaemia (APL) is a hematologic malignancy characterized by the rearrangement of the PML and RARα genes, mostly due to a reciprocal chromosomal translocation t(15;17)(q24;q21). A quick APL diagnosis is essential for starting a prompt suitable therapy. We describe a new rapid diagnostic laboratory approach to detect the PML-RARα rearrangement, which gives clear genetic results within 30 min of hybridization. It combines quick cell harvesting, fluorescence in situ hybridization performed with commercial DNA probe and microwave beams supplied by a domestic microwave oven. Copyright © 2015 John Wiley & Sons, Ltd.
Subject(s)
Chromosomes, Human, Pair 15 , Chromosomes, Human, Pair 17 , Leukemia, Promyelocytic, Acute/genetics , Oncogene Proteins, Fusion/genetics , Translocation, Genetic , DNA Probes , DNA, Neoplasm/analysis , Female , Gene Rearrangement , Humans , Immunophenotyping , In Situ Hybridization , In Situ Hybridization, Fluorescence , Karyotyping , Male , MicrowavesABSTRACT
In a phase II trial, we evaluated chlorambucil and rituximab (CLB-R) as first-line induction treatment with or without R as maintenance for elderly chronic lymphocytic leukemia (CLL) patients. Treatment consisted of eight 28-day cycles of CLB (8 mg/m(2) /day, days 1-7) and R (day 1 of cycle 3, 375 mg/m(2) ; cycles 4-8, 500 mg/m(2) ). Responders were randomized to 12 8-week doses of R (375 mg/m(2) ) or observation. As per intention-to-treat analysis, 82.4% (95% CI, 74.25-90.46%) of 85 patients achieved an overall response (OR), 16.5% a complete response (CR), 2.4% a CR with incomplete bone marrow recovery. The OR was similar across Binet stages (A 86.4%, B 81.6%, and C 78.6%) and age categories (60-64 years, 92.3%; 65-69, 85.2%; 70-74, 75.0%; ≥75, 81.0%). CLB-R was well tolerated. After a median follow-up of 34.2 months, the median progression-free survival (PFS) was 34.7 months (95% CI, 33.1-39.5). TP53 abnormalities, complex karyotype, and low CD20 gene expression predicted lack of response; SF3B1 mutation and BIRC3 disruption low CR rates. IGHV mutations significantly predicted PFS. R maintenance tended towards a better PFS than observation and was safe and most beneficial for patients in partial response and for unmutated IGHV cases. CLB-R represents a promising option for elderly CLL patients.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Aged , Aged, 80 and over , Antibodies, Monoclonal, Murine-Derived/administration & dosage , Chlorambucil/administration & dosage , Disease-Free Survival , Drug Administration Schedule , Female , Humans , Induction Chemotherapy , Leukemia, Lymphocytic, Chronic, B-Cell/pathology , Male , Rituximab , Survival Analysis , Treatment OutcomeABSTRACT
The cytogenetic hallmark of Chronic Myeloid Leukemia (CML) is the presence of Philadelphia (Ph) chromosome, which results from a reciprocal translocation t(9;22)(q34;q11). In this report, we describe a CML patient with no evidence of Ph chromosome but trisomy of chromosome 8 as single cytogenetic abnormality and a typical e14a2 (b3a2) BCR-ABL1 fusion transcript. Fluorescence In Situ Hybridization (FISH) analysis revealed an uncommon signal pattern: the fusion signals were located on both copies of chromosome 22. During the course of the disease the appearance of the p.(Tyr315Ile) mutation was recorded. To the best of our knowledge this is the first Ph chromosome-negative CML case with e14a2 (b3a2) BCR-ABL1 transcript and p.(Tyr315Ile) mutation.
ABSTRACT
We describe an High-grade B-cell lymphoma case, in which a complex translocation t(3;8;14) with effects on the genes BCL6, MYC, and IGH, was detected. This case could be the first double-hit lymphoma with a single chromosome rearrangement causing the double effect with three genes involved.
ABSTRACT
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy with aggressive clinical course and poor prognosis. Diagnosis is based on detection of CD4+ CD56+, CD123high, TCL-1+, and blood dendritic cell antigen-2/CD303+ blasts, together with the absence of lineage specific antigens on tumour cells. In this report we present a case of BPDCN presenting with extramedullary and bone marrow involvement, extensively studied by flow cytometry and immunohistochemistry, who achieved complete remission after acute lymphoblastic leukemia like chemotherapy and allogeneic hematopoietic stem cell transplantation.