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acute lymphocytic leukemia [keywords]
- Human induced pluripotent stem cell-derived B lymphocytes can express sIgM and can be generated via a hemogenic endothelium intermediate. [JOURNAL ARTICLE]
- Stem Cells Dev 2014 Dec 18.
The differentiation of human pluripotent stem cells to the B-cell lymphoid lineage has important clinical applications that include in-vitro modelling of developmental lymphogenesis in health and disease. Here, we first demonstrate the capacity of human induced pluripotent stem cells (hiPSCs) to differentiate into CD144+CD73-CD43/CD235a-, cells, characterised as hemogenic endothelium, and show this population is capable of differentiating to CD10+CD19+ B lymphocytes. We also demonstrate that B lymphocytes generated from hiPSCs are able to undergo full VDJ rearrangement and express surface IgM (sIgM+), thus representating an immature B-cell subset. Efficiency of sIgM expression on the iPS-derived B lymphocytes (c. 5% of CD19+ cells) was comparable with B lymphocytes generated from human umbilical cord blood hematopoietic progenitor cells. Importantly, when assessed by global transcriptional profiling, hiPSC-derived B-cells show a very high level of similarity when compared to their umbilical cord blood derived counterparts, such that from over 47,000 different transcripts, only 45 were significantly different (with a criteria adjusted P value P˂0.05, log FC ˃1.0 or 2.8 fold). This represents a unique in-vitro model to delineate critical events during lymphogeneisis in development and lymphoid diseases such as acute lymphocytic leukemia.
- [Structural and functional peculiarities of lymphocytes from patients with lymphoblastic leukemia]. [English Abstract, Journal Article, Research Support, Non-U.S. Gov't]
- Tsitologiia 2013; 55(6):388-93.
New data on the structure and properties of the cell surface of lymphocytes from the blood of patients with CLL, ALL and ALL at remission stage has been obtained using AFM technologies. It's been shown that, despite the presence of immature lymphocytes in the blood flow of patients with CLL and ALL, the mechanical properties and geometrical parameters of the cells are different. Lymphocytes of CLL patients had an increased volume and higher stiffness, while the cells from the blood of patients with ALL and ALL in remission had decreased stiffness, which allowed the cells to spread on the substrate, thereby the volumes increased due to their reduced height and increased diameter. Identified structural and functional peculiarities of white blood cells from the patients with leukemia can be used for prognosis of the cancer progression.
- [Increased risk of severe acute graft-versus-host disease in low body mass index patients undergoing haploidentical allogeneic stem cell transplantation]. [English Abstract, Journal Article]
- Zhonghua Nei Ke Za Zhi 2014 Sep; 53(9):710-4.
To investigate the impact of body mass index (BMI) before transplantation on clinical outcomes of haploidentical allogeneic stem cell transplantation (allo-HSCT).We performed a retrospective cohort study of 253 adult patients with acute or chronic leukemia who received haploidentical allo-HSCT from August 2008 to September 2011. All conditioning regimens were myeloablative and bulsufan based. Patients were stratified according to BMI values (low BMI group: <18 kg/m(2); normal BMI group: ≥ 18 and < 25 kg/m(2); overweight BMI group: ≥ 25 kg/m(2)). Other possible risk factors correlated with GVHD, relapse, transplant related mortality (TRM) and overall survival (OS) included age and gender of donor and recipient, HLA disparity, relationship between donor and recipient, diagnosis, status of disease, ATG dose in conditioning regime(10 mg/kg , 6 mg/kg), mononuclear cells (MNC), CD(+)34 and CD(+)3 cell amount from granulocyte colony-stimulating factor (G-CSF) primed bone marrow grafts (G-BM) and G-CSF mobilized peripheral blood grafts(G-PB). Cox regression analysis was used to determine the related risk factors.The median age of all 253 patients was 31 (18-56) years, including 128 cases with acute myeloid leukemia (AML), 95 cases with acute lymphocytic leukemia (ALL), and 30 cases with chronic myeloid leukemia (CML). According to primary diseases, 185 patients were classified in the standard -risk group and 68 cases in the high-risk group. Median follow-up time was 929 days (range: 48-1762 days) post-transplantation. Engraftment has been attainted 252 (99.6%) recipients with the median time of granulocyte and platelet recovery 12 days (ranging from 9 to 45 days) and 16 days (ranging from 7 to 180 days), respectively. Cumulative incidences of acute GVHD was 33.2% with median time of 25 days (range: 13-88 days) after transplant. Multivariate analysis identified that low BMI was associated with an increased risk of grade III-IV acute GVHD (HR = 5.736, 95%CI 1.779-18.491, P = 0.003). There was no significant impact of BMI to other manifestations of GVHD, TRM, relapse or OS in different groups.Our findings demonstrate a correlation between pre transplant BMI and clinical outcome post-transplant. Low BMI was associated with increased risk of severe acute GVHD in leukemia patients receiving haploidentical allo-HSCT. Meticulous supportive care pre-transplantation is required for low BMI patients.
- To exenterate or not? An unusual case of pediatric rhinocerebral mucormycosis. [JOURNAL ARTICLE]
- Int J Pediatr Otorhinolaryngol 2014 Dec 3.
Rhinocerebral mucormycosis (RM) is a rare, potentially lethal fungal infection. Traditional teaching encourages aggressive surgical resection until viable bleeding tissue is encountered, often leading to orbital exenteration, skull base resection, and cerebral debridement, in addition to systemic antifungal therapy. We present a 2-year-old male with acute lymphocytic leukemia undergoing chemotherapy presenting with RM and unilateral orbital and intracranial involvement. After aggressive sinonasal debridement, systemic antifungal and hyperbaric oxygen therapies, he recovered without need for further aggressive tissue resection. We report the successful management of invasive orbital and intracranial RM without orbital exenteration or cerebral debridement.
- Minimal change nephrotic syndrome associated with non-hodgkin lymphoid disorders: a retrospective study of 18 cases. [Journal Article]
- Medicine (Baltimore) 2014 Nov; 93(24):350-8.
Few studies have examined the occurrence of minimal change nephrotic syndrome (MCNS) in patients with non-Hodgkin lymphoma (NHL). We report here a series of 18 patients with MCNS occurring among 13,992 new cases of NHL. We analyzed the clinical and pathologic characteristics of this association, along with the response of patients to treatment, to determine if this association relies on a particular disorder. The most frequent NHLs associated with MCNS were Waldenström macroglobulinemia (33.3%), marginal zone B-cell lymphoma (27.8%), and chronic lymphocytic leukemia (22.2%). Other lymphoproliferative disorders included multiple myeloma, mantle cell lymphoma, and peripheral T-cell lymphoma. In 4 patients MCNS occurred before NHL (mean delay, 15 mo), in 10 patients the disorders occurred simultaneously, and in 4 patients MCNS was diagnosed after NHL (mean delay, 25 mo). Circulating monoclonal immunoglobulins were present in 11 patients. A nontumoral interstitial infiltrate was present in renal biopsy specimens from 3 patients without significant renal impairment. Acute kidney injury resulting from tubular lesions or renal hypoperfusion was present in 6 patients. MCNS relapse occurred more frequently in patients treated exclusively by steroid therapy (77.8%) than in those receiving steroids associated with chemotherapy (25%). In conclusion, MCNS occurs preferentially in NHL originating from B cells and requires an aggressive therapeutic approach to reduce the risk of MCNS relapse.
- Bendamustine induced tumor lysis syndrome with acute renal failure in chronic lymphocytic leukemia. [LETTER]
- Indian J Cancer 2014 July-September; 51(3):380-381.
- Tcrδ translocations that delete the Bcl11b haploinsufficient tumor suppressor gene promote atm-deficient T cell acute lymphoblastic leukemia. [Journal Article]
- Cell Cycle 2014 Oct 1; 13(19):3076-82.
ATM is the master regulator of the cellular response to DNA double strand breaks (DSBs). Deficiency of ATM predisposes humans and mice to αβ T lymphoid cancers with clonal translocations between the T cell receptor (TCR) α/δ locus and a 450 kb region of synteny on human chromosome 14 and mouse chromosome 12. While these translocations target and activate the TCL1 oncogene at 14q32 to cause T cell pro-lymphocytic leukemia (T-PLL), the TCRα/δ;14q32 translocations in ATM-deficient T cell acute lymphoblastic leukemia (T-ALL) have not been characterized and their role in cancer pathogenesis remains unknown. The corresponding lesion in Atm-deficient mouse T-ALLs is a chromosome t(12;14) translocation with Tcrδ genes fused to sequences on chromosome 12; although these translocations do not activate Tcl1, they delete the Bcl11b haploinsufficient tumor suppressor gene. To assess whether Tcrδ translocations that inactivate one copy of Bcl11b promote transformation of Atm-deficient cells, we analyzed Atm(-/-) mice with mono-allelic Bcl11b deletion initiating in thymocytes concomitant with Tcrδ recombination. Inactivation of one Bcl11b copy had no effect on the predisposition of Atm(-/-) mice to clonal T-ALLs. Yet, none of these T-ALLs had a clonal chromosome t(12;14) translocation that deleted Bcl11b indicating that Tcrδ translocations that inactivate a copy of Bcl11b promote transformation of Atm-deficient thymocytes. Our data demonstrate that antigen receptor locus translocations can cause cancer by deleting a tumor suppressor gene. We discuss the implications of these findings for the etiology and therapy of T-ALLs associated with ATM deficiency and TCRα/δ translocations targeting the 14q32 cytogenetic region.
- Fusarium brain abscess: case report and literature review. [JOURNAL ARTICLE]
- Mycoses 2014 Dec 5.
Severely immunocompromised patients such as those with haematological malignancies and haematopoietic stem cell transplant recipients are at an increased risk of acquiring invasive mould infections. Fusarium, a ubiquitous fungus, can cause potentially fatal infections in such hosts. It usually manifests as skin lesions, fevers and sino-pulmonary infections. Brain abscesses have been reported, but are relatively uncommon. We report a case of a 50-year-old patient with acute lymphocytic leukaemia and failed autologous peripheral stem cell transplant that presented with new onset seizures and was found to have Fusarium solani brain abscess. Nasal route was the presumed mode of entry of the fungus into the cerebrum. Treatment comprised surgical excision of the lesion, and antimycotic therapy with liposomal amphotericin B and voriconazole. Despite aggressive therapy, patient succumbed to the disease. We have provided an overview of infections secondary to Fusarium, along with a review of the central nervous system involvement by this pathogenic mould.
- Lymphocytic leukemia presenting as acute Vogt-Koyanagi-Harada disease. [Journal Article]
- Saudi J Ophthalmol 2014 Oct; 28(4):319-21.
Leukemia commonly involves eyes and adnexae. It is unusual, however for leukemia to present with visual complaints. There are only rare case reports of a leukemic patient presenting with bilateral exudative retinal detachment. This report describes a case of bilateral exudative retinal detachment associated with prodromal symptoms simulating the presentation of acute Vogt-Koyanagi-Harada disease that was eventually diagnosed as acute lymphocytic leukemia. There was rapid settling of the exudative detachment and improvement in vision when the patient received chemotherapy. Bilateral exudative retinal detachment associated with neurologic and auditory abnormalities may be a presenting sign of acute lymphocytic leukemia in an otherwise healthy young adult. Clinicians should be aware of the possibility of leukemia in such patients. A simple blood investigation such as complete blood profile confirms the diagnosis.
- Ph-like acute lymphoblastic leukemia in older adults. [Comment, Letter]
- N Engl J Med 2014 Dec 4; 371(23):2235.