Linfoma de Burkitt primario de mama durante el embarazo / Primary Burkitt's Lymphoma of the Breast During Pregnancy

El linfoma de Burkitt es una neoplasia altamente agresiva y es un tipo raro de linfoma no Hodgkin localizado. Aunque los niños son los más frecuentemente afectados, en adultos ocurren principalmente durante el embarazo o el puerperio. La mama rara vez constituye la localización primaria del linfoma no Hodgkin. Se presenta un caso de linfoma de Burkitt primario de mama durante el embarazo. Paciente de 37 años con embarazo de 24 semanas quien presentó aumento de volumen difuso de mama derecha. La mama estaba aumentada de tamaño, dolorosa y homogénea con tumoración elástica y firme. La ecografía demostró inflamación difusa con tumoración heterogénea e hipoecoica con contornos ligeramente irregulares, marcadores tumorales estaban normales las pruebas serológicas fueron negativas. La biopsia de la lesión mostró tejido mamario reemplazado por células linfoideas de tamaño mediano con citoplasma basófilo y múltiples vacuolas. Estudios inmunohistoquímicos fueron positivos para el antígeno leucocitario común, CD10, CD20, CD43, Bcl-6. El análisis cromosómico reveló que más del 90 % de las células neoplásicas exhibieron translocación t llevando al diagnóstico final de linfoma de Burkitt de mama. Luego de evaluar las posibilidades terapéuticas y del consentimiento de la paciente se inició tratamiento citostático sistémico. Los linfomas primarios de mama son extremadamente raros. El linfoma de Burkitt primario de la mama es mucho menos común que los otros linfomas. Los métodos de clasificación, detección y tratamiento de esta afección siguen siendo objeto de debates e investigaciones(AU)

The Burkitt's lymphoma is a highly aggressive neoplasm and is a rare type of localized non-Hodgkin lymphoma. Although children are the most frequently affected, in adults they occur mainly during the pregnancy or the puerperium. The breast rarely constitutes the primary location for non-Hodgkin lymphoma. The study of a case of primary Burkitt lymphoma of the breast during pregnancy is presented. This is a 37 year old patient with a 24 week pregnancy who presented a diffuse increase in the volume of the right breast. The breast was enlarged, painful and homogeneous with a firm, elastic mass. The ultrasonography showed diffuse inflammation with a heterogeneous and hypoechoic tumor with slightly irregular contours. The tumor marker values were normal and the serological tests were negative. The biopsy of the lesion showed breast tissue replaced by medium-sized lymphoid cells with basophilic cytoplasm and multiple vacuoles. Immunohistochemically studies were positive for the common leukocyte antigen, CD10, CD20, CD43, Bcl-6. The chromosomal analysis revealed that more than 90 % of neoplastic cells exhibited t translocation leading to the final diagnosis of Burkitt lymphoma of the breast. After evaluating the therapeutic possibilities and the patient's consent, systemic cytostatic treatment was started. Primary breast lymphomas are extremely rare. The primary Burkitt lymphoma of the breast is much less common than other lymphomas. The methods of classification, detection, and the treatment of this condition continue to be the subject of debate and research(AU)

A Case of Pediatric Acute Lymphoblastic Leukemia with Trisomy 5 as a Sole Chromosomal Anomaly: A Prognostic Significance / 임상소아혈액종양

We present a case of Korean pediatric patient with pre-B cell type acute lymphoblastic leukemia (ALL) with trisomy 5 as a sole cytogenetic anomaly. Here, we compare and describe the present case with previous pediatric case reports and provide a review of the literature. This case report may help elucidate the poor prognostic impact of trisomy 5 as a sole cytogenetic anomaly in pediatric patients with ALL. Additional studies are needed to confirm this hypothesis.

Significance of neuropilin-1 expression, ceruloplasmin oxidase and copper in egyptian children with b-lineage acute lymphoblastic leukemia

Background: Neuropilins are transmembrane glycoproteins that act as receptors for vascular endothelial growth factors (VEGF) and are involved in the process of tumor angiogenesis. Ceruloplasmin is a member of the multi copper oxidase family. It has antioxidant properties that play a central role in protection of the body against advanced oxidation protein products.Objective: This study was aimed to assess the expression of Neuropilin-1(NRP-1) on blasts of B-lineage precursor lymphoblastic leukemia (ALL) to be used in the diagnostic panel of this disease. We also aimed to assess the alteration of the levels of ceruloplasmin oxidase and copper as a compensatory mechanism to minimize the effects of reactive oxygen species resulting from leukemias.Subjects and Methods: This study was conducted on 40 children with newly diagnosed B-lineage precursor lymphoblastic leukemia. 40 age-matched controls were enrolled to serve as control. The expression of NRP-1 on peripheral blood samples was evaluated by flow cytometry as the proportion of positive cells expressing the marker. Ceruloplasmin oxidase and copper levels were assessed by immunoturbidimetric assay.Results: There was highly significant increase in the proportion of positivity of NRP -1 in patients compared with control group (P<0.001) Ceruloplasmin oxidase and copper levels were also higher in patients compared with control group (P<0.001).Conclusions: It could be concluded that NRP-1 is a valuable marker for diagnosis of B-lineage ALL. There is an increase in the levels of ceruloplasmin oxidase and copper which at the time of diagnosis of B-ALL

Validation Study of an Operational Tolerance Signature in Korean Kidney Transplant Recipients

Operational tolerance (OT), defined as maintaining stable graft function without immunosuppression after transplant surgery, is an ideal goal for kidney transplant recipients (KTRs). Recent investigations have demonstrated the distinctive features of B cells, T cells, and dendritic cell-related gene signatures and the distributions of circulating lymphocytes in these patients; nonetheless, substantial heterogeneities exist across studies. This study was conducted to determine whether previously reported candidate gene biomarkers and the profiles of lymphocyte subsets of OT could be applied in Korean KTRs. Peripheral blood samples were collected from 153 patients, including 7 operationally tolerant patients. Quantitative real-time PCR and flow cytometry were performed to evaluate gene expression and lymphocyte subsets, respectively. Patients with OT showed significantly higher levels of B cell-related gene signatures (IGKV1D-13 and IGKV4-1), while T cell-related genes (TOAG-1) and dendritic cell-related genes (BNC2, KLF6, and CYP1B1) were not differentially expressed across groups. Lymphocyte subset analyses also revealed a higher proportion of immature B cells in this group. In contrast, the distributions of CD4⁺ T cells, CD8⁺ T cells, mature B cells, and memory B cells showed no differences across diagnostic groups. An OT signature, generated by the integration of IGKV1D-13, IGKV4-1, and immature B cells, effectively discriminated patients with OT from those in other diagnostic groups. Finally, the OT signature was observed among 5.6% of patients who had stable graft function for more than 10 years while on immunosuppression. In conclusion, we validated an association of B cells and their related signature with OT in Korean KTRs.

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.

Characterization of clonal immunoglobulin heavy (IGH) V-D-J gene rearrangements and the complementarity-determining region in South Indian patients with precursor B-cell acute lymphoblastic leukemia

BACKGROUND: This study characterized clonal IG heavy V-D-J (IGH) gene rearrangements in South Indian patients with precursor B-cell acute lymphoblastic leukemia (precursor B-ALL) and identified age-related predominance in VDJ rearrangements. METHODS: IGH rearrangements were studied in 50 precursor B-ALL cases (common ALL=37, pre-B ALL=10, pro-B ALL=3) by polymerase chain reaction (PCR) heteroduplex analysis. Twenty randomly selected clonal IGH rearrangement sequences were analyzed using the IMGT/V-QUEST tool. RESULTS: Clonal IGH rearrangements were detected in 41 (82%) precursor B-ALL cases. Among the IGHV1-IGHV7 subgroups, IGHV3 was used in 25 (50%) cases. Among the IGHD1-IGHD7 genes, IGHD2 and IGHD3 were used in 8 (40%) and 5 (25%) clones, respectively. Among the IGHJ1-IGHJ6 genes, IGHJ6 and IGHJ4 were used in 9 (45%) and 6 (30%) clones, respectively. In 6 out of 20 (30%) IGH rearranged sequences, CDR3 was in frame whereas 14 (70%) had rearranged sequences and CDR3 was out of frame. A somatic mutation in Vmut/Dmut/Jmut was detected in 14 of 20 IGH sequences. On average, Vmut/Dmut/Jmut were detected in 0.1 nt, 1.1 nt, and 0.2 nt, respectively. CONCLUSION: The IGHV3 gene was frequently used whereas lower frequencies of IGHV5 and IGHV6 and a higher frequency of IGHV4 were detected in children compared with young adults. The IGHD2 and IGHD3 genes were over-represented, and the IGHJ6 gene was predominantly used in precursor-B-ALL. However, the IGH gene rearrangements in precursor-B-ALL did not show any significant age-associated genotype pattern attributed to our population.

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.

Effect of Dexamethasone on Blast Composition in Patients with Myelodysplastic Syndrome and Its Diagnostic Significance / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To analyze the effect of dexamethason (Dex) on blast composition in patients with myelodysplastic syndrome (MDS) and investigate its significance in diagnosis of MDS.</p><p><b>METHODS</b>The flow cytometry (FCM) was used to detect the blast rate and the expression of its antigens in 30 cases of MDS (10 cases were treated with Dex as DX group and 20 cases were treated without Dex as control group).</p><p><b>RESULTS</b>The difference of the CD34(+) cell number detected by FCM was not statistically significant between DX group and control group (P > 0.05); The rate of BM B cell precursors (BCP CD34(+)/CD19(+)/CD10(+) cells) increased in DX group significantly, and BM CD117(+) cells in CD34(+) cells was decreased significantly as compared with control group (P < 0.001). The expression of antigens between granulocyte and monocyte was not significantly different (P > 0.05).</p><p><b>CONCLUSION</b>The dexamethasone can increase the rate of BCP significantly and decreased the rate of BM CD117(+) cells in CD34(+) cells significantly. There is significant influence on the blast composition in MDS patients after dexamethasone treatment and without significant influence on the other phenotypcs.</p>

Importancia del estudio de la médula ósea en el Hospital Carlos Andrade Marín en el año 2013 / Importance of the bone marrow study of the year 2013 in Carlos Andrade Marin Hospital

Objetivo: el estudio de la biopsia de la médula ósea tiene como objetivo el diagnosticar los problemas que existen con los diversos tipos de células sanguíneas, con el fin de realizar un tratamiento y obtener un pronóstico adecuados; en el tiempo este exámen ha ido ampliándose y junto con el aspirado ayudan a la evaluación de patologías como anemia, trombocitopenia, linfomas, leucemias, tumores metastáticos, síndromes mieloproliferativos entre otros. Materiales y métodos: estudio retrospectivo, descriptivo y con diseño transversal. Se analizaron 450 muestras obtenidas desde enero a diciembre del 2013 para evaluar las distintas patologías que se presentan frecuentemente en nuestro hospital, de acuerdo a edad y sexo. Resultados: de los 450 casos receptados, analizados y reportados en el 2013; 236 muestras fueron negativas; 27 fueron muestras insuficientes e inadecuadas y 187 fueron positivas para lesiones benignas, borderline y malignas. La mayor parte de lesiones fueron más en hombres y en edades comprendidas entre 40 y 69 años. Las lesiones benignas más frecuentes fue la Hipoplasia y dentro de las lesiones malignas la infiltración linfocitica de inmunofenotipo B, la misma que se corroboró con estudio de Inmunohistoquimica. Conclusión: se determina que de los estudios realizados, la patología que con mayor frecuencia afecta a los pacientes del Hospital Carlos Andrade Marín, sometidos a biopsia de médula ósea en el año 2013 es la Infiltración de estirpe linfoide con biopsy has become important for the treatment and prognosis of diseases. Inmunofenotipo B. De ahí que el estudio de biopsia de médula ósea se ha tornado importante para el tratamiento y pronóstico de las diferentes patologías hematológicas y metastásicas.

Objective: the study of bone marrow biopsy aims to diagnose the problems that exist with the different types of blood cells, with the aim of treatment and obtain an acertive prognosis, with time this test has become popular and together with the aspirate helps with the evaluation of diseases such as anemia, trombocitopenia, leucemias, lymphomas among others, myeloproliferative syndromes, and metastatic tumors. Materials and methods: a retrospective descriptive study with cross-sectional design was used to analyze 450 samples obtained from january to december of 2013 in order to evaluate the different pathologies that arise frequently in our hospital, profiled by age and sex. Results: of the 450 analyzed cases and reported in the 2013; 236 samples were negative; 27 were insufficient and inadequate samples, 187 were positive for benign lesions, borderline or malignant. Most of the lesions were in men aged between 40 and 69 years; Hypoplasia was amongst the most benign lesions and among the malignant lesions was the Immune B Lymphocytic Infiltration, which was corroborated with inmunohistochemical staining. Conclusion: this study determines that the disease which most often affects patients of the Hospital Carlos Andrade Marín undergoing bone marrow biopsy in the year 2013 was lineage with Immune B lymphoid infiltration. Hence the study of bone marrow biopsy has become important for the treatment and prognosis of diseases.

Promoter methylation and expression levels of selected hematopoietic genes in pediatric B-cell acute lymphoblastic leukemia

BACKGROUND: Precursor B-cell acute lymphoblastic leukemia (B-cell ALL) is the most common neoplasm in children and is characterized by genetic and epigenetic aberrations in hematopoietic transcription factor (TF) genes. This study evaluated promoter DNA methylation and aberrant expression levels of early- and late-acting hematopoietic TF genes homeobox A4 and A5 (HOXA4 and HOXA5), Meis homeobox 1 (MEIS1), T-cell acute lymphocytic leukemia 1 (TAL1), and interferon regulatory factors 4 and 8 (IRF4 and IRF8) in pediatric B-cell ALL. METHODS: Blood samples of 38 ALL patients and 20 controls were obtained. DNA was treated with sodium bisulfite and DNA methylation level of HOXA4, HOXA5, MEIS1, TAL1, IRF4, and IRF8 was assessed using quantitative methylation-specific polymerase chain reaction (PCR). Relative gene expression was measured using quantitative reverse transcription-PCR. RESULTS: Aberrant methylation of TAL1, IRF8, MEIS1, and IRF4 was observed in 26.3%, 7.9%, 5.3%, and 2.6% patients, respectively, but not in controls. HOXA4 and HOXA5 were methylated in some controls and hypermethylated in 16% and 5% patients, respectively. IRF8, MEIS1, and TAL1 expression was lower in patients than in controls. MEIS1 expression was inversely correlated with white blood cell (WBC) count. HOXA4 expression was down-regulated in patients with high risk according to the National Cancer Institute (NCI) classification. TAL1 methylation was slightly elevated in patients aged >9 years and in patients showing relapse, suggesting its potential prognostic value. CONCLUSION: Aberrant methylation and expression of the selected hematopoietic genes were correlated with demographic/clinical prognostic factors of pediatric ALL, such as age, WBC count, and NCI risk classification.

Influence of calcineurin on apoptosis of pre-B lymphocytes and the leukemia cells derived from pre-B lymphocytes / 中国实验血液学杂志

This study was aimed to compare the differential expressions of calcineurin (PP2B, PP3) in the mouse Pre-B cell lines (S9) and the tumor cell lines (S4C2) derived from pre-B lymphocytes, and to clarify its possible mechanism involving in the leukemia cell apoptosis. The quantitative real-time PCR was used to detect the differential expressions of H2AX-associated phosphakinase ATM, ATR, DNA-PKs, JNK1, P38 and the γ-H2AX-related phosphatase PP1, PP2A, calcineurin, PP4, PP6, PP5 between S9 and S4C2 cell lines. CCK-8 assay and flow cytometry were used to detect the effect of imatinib (IM) and cyclosporine A (CsA) on cytotoxicity and apoptosis of 2 cell lines. The Western blot was used to detect the effects of 2 drugs on apoptosis of S9 and S4C2 cell lines. The results showed that the expression level of calcineurin gene in the leukemia cell S4C2 was about 3.5 times of that in S9 cells, while the expression of other genes in these 2 kinds of cells was not significantly different. The apoptosis and toxicity of IM and CsA on S4C2 cells was significantly stronger than that on S9 cells. The expression level of calcineurin in S4C2 cells was higher than that in S9 cells.When CsA inhibited the calcineurin activity, the expression of DNA damage marker γ-H2AX in S9 cells was significantly lower than that in S4C2 cells,while the expression level of γ-H2AX between the two cell lines was no significantly different after treatment with imatinib, the expression level of γ-H2AX in S9 cells was lower than that in S4C2 cells when the two drugs were combined. It is concluded that the calcineurin plays a role of anti-apoptosis in B leukemic cells, cyclosporine A can promote the leukemia cell apoptosis.

Analysis and significance of hematopoietic progenitor B cells in patients with acute leukemia / 中国实验血液学杂志

Normal hematopoietic B progenitor cells are similar with acute B lymphoblastic leukemia (ALL) cells in terms of morphology and immunophenotypes which easily result in misdiagnosis of diseases. This study was purposed to explore the importance of B progenitor cell (BPC) level in differential diagnosis of hematologic diseases. A total of 664 specimens including 87 specimens from patients with non-malignant hematologic diseases as control and 577 specimens from AL patients in different progressive stage were analyzed. Out of 577 specimens 26 were collected from ALL patients, 261 were collected from B-ALL, 290 were collected from AML. The relation of different clinical status (new diagnosis, remission, relapse), age and degree of leukemia cell involvement with hematopoietic BPC level were analyzed through identification of CD34/CD10/CD19/CD45 antibody combination and quantification of hematopoietic BPC. The results indicated that (1) CD45 distributed from positive to weak positive, and with very low side scatter. The early hematopoietic BPC expressed CD34⁺, along with increasing of cell maturation, the CD34 expression gradually disappeared, while CD19 and CD10 showed positive in whole stage of hemaropoietic BPC, and early CD10 highly was expressed. (2) the mean percentage of hematopoietic BPC was 1.36% in control group, 0.60% in T-ALL, 1.39% in B-ALL and 0.80% in AML; the detected rate of hematopoietic BPC in control, T-ALL, B-ALL and AML were 87.4%, 61.5%, 83.5%, 75.9%, respectively; the mean percentage of hematopoietic BPC was 0.37% at new diagnosis, 1.66% in remission and 0.55% in relapse. (3) along with increase of age, the hematopoietic BPC level generally disclined. (4) specimens >5% hematopoietic BPC were mainly found in remission stage of leukemia patients. It is concluded that the hematopoietic BPC are present in malignant and non-malignant hematologic diseases. The changes of hematopoietic BPC level correlate with disease state, age and leukemia cell involvement. The increased hematopoietic BPC level are observed most often in the patients with remission after themotherapy. It should be carefully to diagnose and discriminate between malignant and benign cells with double positive CD19 and CD10. Use of multiparametric flow cytometry and optimal antibody combination are important for discriminating hematopoietic BPC from minor residual disease and accuratly diagnosing diseases and evaluating curative effectiveness.

Distribution of CD10-positive epithelial and mesenchymal cells in human mid-term fetuses: a comparison with CD34 expression / 대한해부학회지

CD10, a marker of immature B lymphocytes, is expressed in the developing epithelium of mammary glands, hair follicles, and renal tubules of human fetuses. To assess mesenchymal and stromal expression of CD10, we performed immunohistochemical assays in whole body sections from eight fetuses of gestational ages 15-20 weeks. In addition to expression in urinary tract and intestinal epithelium, CD10 was strongly expressed at both gestational ages in fibrous tissues surrounding the airways from the larynx to lung alveoli, in the periosteum and ossification center, and in the glans of external genitalia. CD10 was not expressed, however, in other cavernous tissues. These findings suggest that mesenchymal, in addition to epithelial cells at specific sites, are likely to express CD10. The glomeruli, alveoli, and glans are all end products of budding or outgrowth processes in the epithelium or skin. However, in contrast to the CD34 marker of stromal stem cells, CD10 was not expressed in vascular progenitor cells and in differentiated vascular endothelium. The alternating pattern of CD10 and CD34 expression suggests that these factors play different roles in cellular differentiation and proliferation of the kidneys, airway and external genitalia.

Isolated Central Nervous System Relapse of Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common form of childhood cancer and may exhibit central nervous system (CNS) involvement. Advances in chemotherapy and effective CNS prophylaxis have significantly decreased the incidence of CNS relapse of ALL to 5-10%. Here, we report the case of a patient with isolated CNS relapse of standard risk group pre-B-cell type ALL in an 11-year-old girl, relapsed 3 years after successful completion of chemotherapy. An 11-year-old girl visited our hospital complaining of headache, dizziness, vomiting, and visual field defects. Neurological examination revealed left-side homonymous hemianopsia. Brain magnetic resonance imaging showed a large irregular dural-based sulcal hematoma in the right parietal and occipital lobes. Surgery to remove the hematoma revealed the existence of hematopoietic malignancy after pathologic evaluation. Bone marrow biopsy was subsequently performed but showed no evidence of malignancy.

Mesenchymal stem cells promote leukaemic cells aberrant phenotype from B-cell acute lymphoblastic leukaemia

The role of bone marrow-mesenchymal stem cells [BM-MSC] in leukaemic cell control is controversial. The purpose of this work was to evaluate BM-MSC role regarding the viability, proliferation and immunophenotype of normal B-cell precursors from control [Ct] patients and leukaemic cells from B-acute lymphoblastic leukaemia [B-ALL] patients. BM-MSC were isolated and characterised from voluntary donors. Mononuclear cells isolated from Ct and B-ALL bone marrow samples were cultured in the presence or absence of BM-MSC for 7 days. Cell viability was determined with LIVE/DEAD and proliferation index evaluated by CFSE labelling. Cell population immunophenotypes were characterised by estimating CD19, CD10, CD20 and CD45 antigens by flow cytometry. After co-culture, B-ALL cells exhibited higher viability [20-40%] as compared to just cells [3-10%]. Ct and B-ALL absolute cell counts were higher in the presence of BM-MSC [Ct: 25/mm[3] cf 8/mm[3], B-ALL: 15/mm[3] cf 3/mm[3]]. Normal B-cell subpopulations in co-culture had increased expression of CD19 and CD10 [Pre-pre B] and CD45 and CD20 antigens [Pre-B]. B-ALL cells co-cultured with BM-MSC showed an increase in CD19 and CD20, although the greatest increase was observed in the CD10 antigen. Lymphoid cell maintenance, at early stages of differentiation, was significantly promoted by BM-MSC in normal and leukaemic cells. Co-cultures also modulated the expression of antigens associated with the B-ALL asynchronous phenotype as CD10 co-expressed with CD19 and CD20. To our knowledge, this is the first time that CD10, CD19 and CD20 leukaemic antigens have been reported as being regulated by BM-MSC

Precursor B-Cell Acute Lymphoblastic Leukemia in Two Patients with a History of Cytotoxic Therapy / 대한내과학회지

Therapy-related myeloid neoplasms have been well characterized. However, precursor B-cell acute lymphoblastic leukemia in patients with prior malignancies is uncommon, and the effect of prior cytotoxic therapy on development of precursor B-cell acute lymphoblastic leukemia is controversial. Therapy-related precursor B-cell acute lymphoblastic leukemia has been reported occasionally. However, cytotoxic therapy-related precursor B-cell acute lymphoblastic leukemia has been reported in Korea only rarely. We herein describe two cases of therapy-related precursor B-cell acute lymphoblastic leukemia.

Swiprosin-1 Expression Is Up-Regulated through Protein Kinase C-theta and NF-kappaB Pathway in T Cells

Swiprosin-1 exhibits the highest expression in CD8+ T cells and immature B cells and has been proposed to play a role in lymphocyte biology through actin remodeling. However, regulation of swiprosin-1 gene expression is poorly understood. Here we report that swiprosin-1 is up-regulated in T cells by PKC pathway. Targeted inhibition of the specific protein kinase C (PKC) isotypes by siRNA revealed that PKC-theta is involved in the expression of swiprosin-1 in the human T cells. In contrast, down-regulation of swiprosin-1 by A23187 or ionomycin suggests that calcium-signaling plays a negative role. Interestingly, swiprosin-1 expression is only reduced by treatment with NF-kappaB inhibitors but not by NF-AT inhibitor, suggesting that the NF-kappaB pathway is critical for regulation of swiprosin-1 expression. Collectively, these results suggest that swiprosin-1 is a PKC-theta-inducible gene and that it may modulate the late phase of T cell activation after antigen challenge.

Increased HoxB4 Inhibits Apoptotic Cell Death in Pro-B Cells

HoxB4, a homeodomain-containing transcription factor, is involved in the expansion of hematopoietic stem cells and progenitor cells in vivo and in vitro, and plays a key role in regulating the balance between hematopoietic stem cell renewal and cell differentiation. However, the biological activity of HoxB4 in other cells has not been reported. In this study, we investigated the effect of overexpressed HoxB4 on cell survival under various conditions that induce death, using the Ba/F3 cell line. Analysis of phenotypical characteristics showed that HoxB4 overexpression in Ba/F3 cells reduced cell size, death, and proliferation rate. Moreover, the progression from early to late apoptotic stages was inhibited in Ba/F3 cells subjected to HoxB4 overexpression under removal of interleukin-3-mediated signal, leading to the induction of cell cycle arrest at the G2/M phase and attenuated cell death by Fas protein stimulation in vitro. Furthermore, apoptotic cell death induced by doxorubicin-treated G2/M phase cell-cycle arrest also decreased with HoxB4 overexpression in Ba/F3 cells. From these data, we suggest that HoxB4 may play an important role in the regulation of pro-B cell survival under various apoptotic death environments.

Patogénesis de la leucemia linfática crónica / Pathogenesis of the chronic lymphocytic leukemia

La leucemia linfática crónica (LLC) es la leucemia de mayor prevalencia en adultos mayores. Se caracteriza por la acumulación progresiva de linfocitos B con morfología madura y un fenotipo particular con expresión de CD5, CD23 y bajos niveles de inmunoglobulina en la membrana. El linfocito leucémico en LLC presenta numerosas aberraciones cromosómicas, pero no se ha podido atribuir a una mutación o deleción particular la responsabilidad de la transformación maligna. Las alteraciones epigenéticas también juegan un papel en LLC, en particular la baja o nula expresión de ciertos microARN que controlan la transcripción de genes anti-apoptóticos. La inmunoglobulina clonal en LLC representa una molécula clave para entender la patología. Alrededor del 30% de los pacientes expresan inmunoglobulinas que reconocen autoantígenos intracelulares que se exponen en las células apoptóticas. En estos casos, la estimulación a través del receptor antigénico sería la responsable de la iniciación y/o progresión leucémica. Tradicionalmente se consideró a la LLC como una patología causada por defectos en la maquinaria apoptótica. En años recientes se demostró que las células leucémicas proliferan en forma activa en los tejidos linfáticos, donde se encuentran en íntimo contacto con linfocitos T, células estromales y de estirpe mieloide. Este microambiente particular provee a las células LLC de señales de supervivencia y activación a través de factores solubles y contacto celular. Uno de los objetivos terapeúticos actuales es lograr compuestos que rompan la interacción de las células LLC con su microambiente para interferir con estas señales de supervivencia. En esta revisión se discuten los aportes realizados desde la investigación básica para entender la etiopatología de la LLC.

Chronic lymphocytic leukemia (CLL) is the commonest leukemia in elderly. It is characterized by the progressive accumulation of B lymphocytes, with a mature morphology and a particular phenotype, expressing CD5, CD23 and low levels of surface immunoglobulin. Although the leukemic lymphocyte in CLL presents a variety of chromosomic aberrations, none of them was demonstrated to be responsible for the malignant transformation. Epigenetic alterations have also a place in CLL, particularly the low or absent expression of a number of microRNA that normally control the transcription of anti-apoptotic genes. Around 30% of CLL cases express clonal immunoglobulin that recognizes intracellular autoantigens which are exposed in apoptotic cells. In these cases, stimulation through the antigenic receptor would be responsible for the initiation and/or progression of the disease. The traditional point of view considered CLL as a pathology caused by defects in the apoptotic machinery. However, in recent years it was demonstrated that leucemic cells actively proliferate in lymphoid tissues, where they are found in intimate contact with T lymphocytes, myeloid and stromal cells. This particular microenvironment provides CLL cells with survival and activation signals through the release of soluble factors and cell contact interactions. Today, one of the therapeutic goals in CLL is the development of agents capable of disturbing the interaction of leukemic cells with their mileu in order to interfere with pro-survival signals. This review discusses the novel evidence from basic research directed to understand the etiopathology of CLL.

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.