Application of targeted capture high depth sequencing and transcriptome sequencing in childhood B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To investigate the differences among targeted capture high depth sequencing (Panel-seq), transcriptome sequencing (RNA-seq) and traditional detection methods in cytogenetic and molecular genetic typing of childhood B-cell acute lymphoblastic leukemia (B-ALL) and their significances.Methods:The clinical data of 152 newly diagnosed childhood B-ALL cases in Guangzhou Women and Children's Medical Center from September 2020 to December 2021 were retrospectively analyzed. Along with traditional cytogenetic and molecular detection methods including karyotyping, fluorescence in situ hybridization (FISH) and 43 kinds of fusion gene quantitative screening for traditional cells and molecular genetic detection, both Panel-seq and RNA-seq were also performed. Panel-seq covered more than 600 genes with common mutations in hematological tumors, from which fusion genes and gene mutations were both analyzed. RNA-seq was used to analyze fusion genes, gene mutations, gene expression, and copy number variation at the chromosome level. High hyperdiploid karyotype was estimated by using gene expression profile clustering and copy number variations. The cytogenetic typing results of all detection methods were also analyzed.Results:Among 152 patients, 93 cases were males and 59 cases were females, with the median age of 4.0 years (0.8-13.0 years). The median blast cell ratio was 0.855 (0.215-0.965). The traditional detection methods could identify 4 cases (2.6%) with BCR-ABL1, 2 cases (1.3%) with CRLF2 gene-related fusion, 27 cases (17.8%) with ETV6-RUNX1, 1 case (0.7%) with iAMP21, 5 cases (3.3%) with MLL rearrangement, 8 cases (5.3%) with TCF3-PBX1 and 22 cases (14.5%) with high hyperdiploid karyotype. Panel-seq could identify 4 cases (2.6%) with BCR-ABL1, 2 cases (1.3%) with CRLF2 gene-related fusions, 27 cases (17.8%) with ETV6-RUNX1, 3 cases (2.0%) with MEF2D gene-related fusions, 1 case (0.7%) with MEIS1-FOXO1, 5 cases (3.3%) with MLL rearrangement, 5 cases (3.3%) with PAX5 gene-related fusions, 8 cases (5.3%) with TCF3-PBX1 fusions, 4 cases (2.6%) with ZNF384 gene-related fusions, and 2 cases (1.3%) with IKZF1 N159Y mutations. Among 152 patients, 1 case with MLL rearrangement didn't receive RNA-seq detection because of sample quality; in other 151 B-ALL cases, 1 case (0.7%) with ACIN1-NUTM1, 4 cases (2.6%) with BCR-ABL1, 3 cases (2.0%) with CRLF2 gene-related fusions, 8 cases (5.3%) with DUX4 gene-related fusions, 27 cases (17.9%) with ETV6-RUNX1, 3 cases (2.0%) with MEF2D gene-related fusions, 1 case (0.7%) with MEIS1-FOXO1, 4 cases (2.6%) with MLL rearrangement, 5 cases (3.3%) with PAX5 gene-related fusions, 1 case (0.7%) with ZMIZ1-ABL1, 8 cases (5.3%) with TCF3-PBX1,4 cases (2.6%) with ZNF384 gene-related fusions, 61 cases (40.4%) with hyperdiploid karyotypes, and 2 cases (1.3%) with IKZF1 N159Y mutations were detected; RNA-seq had obvious advantage in detecting fusion gene and hyperdiploid karyotype. The cytogenetic and molecular genetic typing rates of traditional method, Panel-seq and RNA-seq were 45.4% (69/152), 40.1% (61/152) and 87.4% (132/151), respectively. The combination of the three could identify 89.5% (136/152) of childhood B-ALL patients.Conclusions:The combination of Panel-seq and RNA-seq can increase the detection rate of genetic abnormality in childhood B-ALL, which provides a more accurate molecular genetic classification for B-ALL and the basis for treatment guideline and prognosis judgement.

Immunophenotypic characterization of acute leukemias in Bahia, Brazil

ABSTRACT Objective To characterize the immunophenotypic profile of acute leukemias in the population of the state of Bahia, Brazil. Methods This is a descriptive, retrospective study. From 2014 to 2018, 796 new cases of acute leukemia were evaluated. The data were obtained from analysis of reports and records of tests performed by flow cytometry immunophenotyping. All individuals of all age groups diagnosed as acute lymphoblastic leukemia or acute myeloid leukemia were included in the study. Demographic variables and expression of leukemia antigens were evaluated. Results Most cases were diagnosed as acute myeloid leukemia and 42.7% as acute lymphoblastic leukemia. Significant differences were found in expression of markers in acute leukemias when age groups were compared, as well as in demographic characteristics. B-cell acute lymphoblastic leukemia was more prevalent than cases of T-cell origin. Assessing the aberrant markers in acute myeloid leukemias, the non-acute promyelocytic leukemia group presented expression of CD7 and CD56 as the most frequent ones. In B-cell acute lymphoblastic leukemia, the most frequent aberrant markers were CD66c, CD13 and CD33. Conclusion Significant differences were found as to several antigens when comparing adults and children, and these findings may contribute to future studies correlating the phenotypic profile to genetic characteristics and therapeutic response, including specific antigen therapies, which may be better targeted.

Linfomas de estirpe B: bases para su entendimiento / Line B lymphomas: understanding their bases

Propósito de la revisión: el objetivo de la revisión es delinear la fisiopatología de los linfomas de estirpe B.Buscamos reportes endonde se incluyela descripción del origen de los Linfomas B para una mejor comprensión de esta patología, a la luz de los avances en las diferentes áreas. Recientes hallazgos: El Grupo Euroflow ha publicado una lista de paneles de Expresión de Antígenos de Superficie en Linfoma no Hodgkin, cuya lista se presenta en este artículo. Extracto: Las neoplasias hematológicas han tenido grandes avances en los últimos años en varios campos, evolucionando desde la identificación citológica, pasando por su caracterización inmunofenotípica por medio de la Citometría de Flujo e Inmunohistoquímica y llegando a la caracterización molecular, iniciando por Técnicas de Cariotipo Convencional, continuando por técnicas de Inmunohibridación in situ y actualmente con la identificación molecular por medio de la Secuenciación de Nueva Generación. Esta es la razón por la que los sistemas de estadificación han ido evolucionando también, siendo el que está al momento en vigencia el propuesto por la Organización Mundial de la Salud en el año 2016.Los linfomas constituyen un grupo heterogéneo de neoplasias hematológicas con un amplio espectro de presentación clínica, cuyo origen se encuentra en los precursores de linfoides y que afectan a los diversos órganos linfoides. De estos, los linfomas dela línea B son los más comunes, motivo de esta revisión

Purpose of the review: the objective of the review is to delineate the pathophysiology of B-line lymphomas. We are looking for reports that include a description of the origin of B-lymphomas for a better understanding of this pathology, in light of advances in the different areas. Recent Findings: The Euroflow Group has published a list of Surface Antigen Expression panels in Non-Hodgkin Lymphoma, the list of which is presented in this article. Extract: Hematological neoplasms have had great advances in recent years in several fields, evolving from cytological identification, passing through their immunophenotypic characterization through Flow Cytometry and Immunohistochemistry and reaching molecular characterization, starting with Conventional Karyotype Techniques , continuing with in situ Immunohybridization techniques and currently with molecular identification through New Generation Sequencing. This is the reason why staging systems have also evolved, the one currently in force being the one proposed by the World Health Organization in 2016. Lymphomas constitute a heterogeneous group of hematological neoplasms with a wide spectrum of clinical presentation, originating from lymphoid precursors and affecting the various lymphoid organs. Of these, line B lymphomas are the most common, which is the reason for this review

Acute lymphoblastic leukemia: primary bone manifestation with hypercalcemia in a child / Leucemia linfoblástica aguda: manifestação óssea primária com hipercalcemia em criança

ABSTRACT Primary bone manifestation associated with hypercalcemia is an infrequent presentation of acute lymphoblastic leukemia (ALL) in children. An 8-year-old girl was admitted with bone and abdomen pain, vomiting, fever, headache, anemia, elevated serum calcium and normal parathyroid hormone levels. Bone radiographs: osteolytic lesions. Bone marrow biopsy showed an infiltration by ALL with immunohistochemical positivity for CD45, CD20, CD79a, TdT and CD10, clinically characterized by hypercalcemia, multifocal osteolytic lesions and single cytopenia. Bone marrow biopsy was a relevant aid in establishing the diagnosis of multifocal osteolytic lesions, associated with hypercalcemia.

RESUMO Apresentação óssea primária associada à hipercalcemia é manifestação clinicolaboratorial infrequente de leucemia linfoblástica aguda (LLA) em crianças. Relatamos o caso de uma criança do sexo feminino, 8 anos, admitida com dores ósseas e no abdômen associadas a vômitos, febre, cefaleia, anemia, hipercalcemia e níveis de paratormônio normais. Radiografias ósseas apresentaram lesões osteolíticas. Biópsia de medula óssea demonstrou infiltração por LLA com positividade imuno-histoquímica para CD45, CD79a, TdT e CD10, clinicamente caracterizada por hipercalcemia, lesões osteolíticas multifocais e citopenia única. A biópsia de medula óssea é importante ferramenta no estabelecimento do diagnóstico de lesões osteolíticas multifocais associada à hipercalcemia.

A Case of Pediatric Precursor B-cell Acute Lymphoblastic Leukemia Associated with Translocations (14;18)(q32;q21) and (8;9)(q24;p13) / 임상소아혈액종양

Precursor B-cell acute lymphoblastic leukemia (ALL), which is the most common subtype of pediatric acute leukemia, generally has a good prognosis. However, the prognosis also depends on the genetic abnormalities of the leukemic blast. Concurrent MYC and IGH/BCL2 translocations have recently been reported as a “double hit” in adult patients, but non-immunoglobulin (non-IG)/MYC translocation has rarely been reported. In this paper, we report a case of pediatric precursor B-cell ALL associated with translocations (14;18)(q32;q21) and (8;9)(q24;p13). The patient was a previously healthy 13-year-old boy. Complete remission was not achieved after first-line four-drug induction chemotherapy; thus, intensive salvage regimen, including high-dose cytarabine and L-asparaginase, were administered, which resulted in morphologic remission. However, his disease relapsed during the second cycle of salvage regimen, and he died of sepsis-induced multiorgan failure.

A Case of Pediatric Precursor B-cell Acute Lymphoblastic Leukemia Associated with Translocations (14;18)(q32;q21) and (8;9)(q24;p13) / 임상소아혈액종양

Precursor B-cell acute lymphoblastic leukemia (ALL), which is the most common subtype of pediatric acute leukemia, generally has a good prognosis. However, the prognosis also depends on the genetic abnormalities of the leukemic blast. Concurrent MYC and IGH/BCL2 translocations have recently been reported as a “double hit” in adult patients, but non-immunoglobulin (non-IG)/MYC translocation has rarely been reported. In this paper, we report a case of pediatric precursor B-cell ALL associated with translocations (14;18)(q32;q21) and (8;9)(q24;p13). The patient was a previously healthy 13-year-old boy. Complete remission was not achieved after first-line four-drug induction chemotherapy; thus, intensive salvage regimen, including high-dose cytarabine and L-asparaginase, were administered, which resulted in morphologic remission. However, his disease relapsed during the second cycle of salvage regimen, and he died of sepsis-induced multiorgan failure.

Outcome of children and adolescents with lymphoblastic lymphoma / Evolução de crianças e adolescentes com linfoma linfoblástico

Summary Introduction: lymphoblastic lymphoma (LBL) is the second most common subtype of non-Hodgkin lymphoma in children. The aim of this study was to characterize the clinical course of children and adolescents with LBL treated at a tertiary center. Methods: this is a retrospective cohort study of 27 patients aged 16 years or younger with LBL admitted between January 1981 and December 2013. Patients were treated according to the therapy protocol used for acute lymphoblastic leucemia. Diagnosis was based on biopsy of tumor and/or cytological examination of pleural effusions. The overall survival was analyzed using the Kaplan-Meier method. Results: the median age at diagnosis was 11.6 years (interquartile range, 4.6- 13.8). LBL had T-cell origin in 16 patients (59%). The most common primary manifestation in T-cell LBL was mediastinal involvement, in 9 patients (56%). Intra-abdominal tumor was the major site of involvement in patients with precursor B-LBL. Most patients had advanced disease (18 patients – 67%) at diagnosis. Twenty-four patients (89%) achieved complete clinical remission. After a median follow-up of 43 months (interquartile range, 6.4-95), 22 patients (81%) were alive in first complete remission. Five children (18.5%) died, three of them soon after admission and two after relapsing. The probability of survival at five years for 20 patients with de novo LBL was 78% (SD 9.4). Conclusion: our findings confirm the favorable prognosis of children with LBL with an intensive chemotherapy regimen derived from ALL therapy.

Resumo Objetivos: linfoma linfoblástico (LL) é o segundo subtipo mais comum de linfoma não Hodgkin em crianças. O objetivo deste estudo foi caracterizar a evolução clínica de crianças e adolescentes com LL em um centro terciário. Métodos: estudo de coorte retrospectivo de 27 pacientes com idade de até 16 anos com LL admitidos entre janeiro de 1981 e dezembro de 2013. Os pacientes foram tratados de acordo com o protocolo de tratamento para leucemia linfoblástica aguda (LLA). O diagnóstico foi baseado em biópsia do tumor e/ou no exame citológico de derrame pleural. A sobrevida global foi analisada pelo método de Kaplan-Meier. Resultados: a média de idade ao diagnóstico foi de 11,6 anos (variação interquartil, 4,6-13,8). Linfoma linfoblástico de células T foi identificado em 16 pacientes (59%) e a manifestação primária mais comum foi o acometimento mediastinal (56%). Tumor intra-abdominal foi a manifestação clínica principal nos pacientes com LL de células pré- -B. A maioria dos pacientes apresentava doença avançada (18 pacientes, 67%) ao diagnóstico. Vinte e quatro pacientes (89%) alcançaram remissão clínica completa. Após um período de acompanhamento médio de 43 meses (intervalo interquartil, 6,4-95), 22 pacientes (81%) continuam vivos em primeira remissão clínica completa. Cinco crianças (18,5%) morreram, três delas logo após a admissão e duas após recidiva. A probabilidade de sobrevida em cinco anos para 20 pacientes com LL de novo foi de 78% (DP 9,4). Conclusão: os resultados confirmam o prognóstico favorável de crianças com LL tratadas com regime de quimioterapia intensiva derivado da terapia de LLA.

Actinomicosis vs Linfoma: presentación de un caso / Actinomycosis vs. lymphoma: a case presentation

Fundamento: el linfoma es la proliferación monoclonal neoplásica de células linfoides en localizaciones del sistema inmunitario, que incluyen ganglios linfáticos, médula ósea, bazo, hígado y tracto gastrointestinal. Caso Clínico: se presentó el caso de Linfoma no Hodgkin linfoblástico de alto grado de malignidad, en una paciente de 36 años de edad con antecedentes de hepatitis viral, giardiasis y aborto provocado con implantación de dispositivo intrauterino, que ingresa en el servicio de terapia intensiva del Hospital Universitario Manuel Ascunce Domenech por ausencia de apetito, decaimiento y pérdida de peso de 30 libras aproximadamente en tres meses; en la exploración física inicial se encuentran grandes edemas blandos en miembros inferiores y caquexia, además de distensión abdominal. Después de una estadía prolongada y tórpida evolución, la paciente fallece.

Background: lymphoma is the proliferation of neoplastic monoclonal of lymphoid cells in locations of the immune system, including lymph nodes, bone marrow, spleen, liver and gastrointestinal tract. Clinical case: is presented a case of a lymphoblastic non-Hodgkin´s lymphoma´s of high-grade of malignancy in a 36-year-old patient with a history of viral hepatitis, giardiasis and abortion caused by implantation of intra-uterine device, admitted in the intensive care unit service at Manuel Ascunce Domenech University Hospital by lack of appetite, dwindles, weight loss of 30 pounds approximately in three months, and in the initial physical examination are found large soft edema in lower limbs and cachexia and abdominal distention. After a long stay and torpid evolution, the patient died.

Primary cutaneous B-cell lymphoblastic lymphoma in an elderly man / 대한혈액학회지

Precursor B-cell lymphoblastic lymphoma (B-LBL) is an uncommon high-grade neoplasm of immature B cells. It occurs predominantly in childhood with extranodal involvement such as skin and bone. Therefore, primary cutaneous involvement in elderly adults is a very rare manifestation of B-LBL. Here, we report a 78-year-old man with B-LBL presenting as a single cutaneous lesion which was immunohistochemically positive for leukocyte common antigen (LCA), CD79a, paired box 5 (PAX5), B cell lymphoma-2 (bcl-2), and terminal deoxynucleotidyl transferase (TdT) staining, but was without systemic involvement. The patient was treated using cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP), and achieved complete response (CR) at the first response assessment conducted after 3 CHOP cycles. After an additional cycle of CHOP treatment, radiotherapy was administered at a total dose of 3,600 cGy over 4 weeks. At the 21-month follow-up, he had maintained CR.

A Case of Pneumatosis Intestinalis in Refractory Acute Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / 대한내과학회지

Pneumatosis intestinalis (PI) is an imaging phenomenon that represents air in the bowel wall. The cause of PI is variable, although specific etiologic factors remain unknown. It is an infrequent complication in leukemia patients and is associated with several medical and surgical conditions. PI often represents a benign condition, but it can also require surgery. Therefore, the assessment of PI with or without complications can be difficult. Herein, we report on an unusual case of a 63 year-old woman with refractory acute precursor B-cell lymphoblastic leukemia-lymphoma who presented with PI resulting from the leukemic process, and finally expired due to sepsis.

Erythroleukemia Relapsing as Precursor B-cell Lymphoblastic Leukemia / 대한진단검사의학회지

AML relapsing as ALL has rarely been reported. We describe the case of a 62-yr-old man who was diagnosed with erythroleukemia with a complex karyotype and achieved complete hematologic and cytogenetic remission after induction chemotherapy. However, 4 months after the initial diagnosis, he showed relapse with blasts showing a different morphology and immunophenotype and was diagnosed with precursor B-cell ALL. The relapsing precursor B-cell ALL presented with the same leukemic clones as the primary erythroleukemia. Cytogenetic analysis of his bone marrow (BM) at the time of the primary erythroleukemia showed complex karyotypic abnormalities, including monosomy 5 and monosomy 7. At relapse, his BM showed reemergence of these leukemic clones of complex karyotypic abnormalities with clonal switch. To our knowledge, this is the first case of a lineage switch from erythroleukemia to ALL.