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PubMed2004

Seizure outcome after anterior temporal lobectomy and its predictors in patients with apparent temporal lobe epilepsy and normal MRI.

PURPOSE: Very little reliable information is available regarding the role of anterior temporal lobectomy (ATL), optimal presurgical evaluation strategy, post-ATL seizure outcome, and the factors that predict the outcome in patients with medically refractory temporal lobe epilepsy (TLE) and normal high-resolution magnetic resonance imaging (MRI). To be cost-effective, epilepsy surgery centers in developing countries will have to select candidates for epilepsy surgery by using the locally available technology and expertise. METHODS: We reviewed the electroclinical and pathological characteristics and seizure outcome of 17 patients who underwent ATL for medically refractory TLE after being selected for ATL based on a noninvasive selection protocol without the aid of positron emission tomography (PET) or single-photon emission computed tomography (SPECT), despite a normal preoperative high-resolution MRI. RESULTS: Seven (41%) patients achieved an excellent seizure outcome; five of them were totally seizure free. An additional five (29%) patients had >75% reduction in seizure frequency. The following pre-ATL factors predicted an excellent outcome: antecedent history of febrile seizures, strictly unilateral anterior temporal interictal epileptiform discharges (IEDs), and concordant type 1 ictal EEG pattern. All the five patients with pathologically verified hippocampal formation neuronal loss were seizure free. The presence of posterior temporal, bilateral temporal, and generalized IEDs portended unfavorable post-ATL seizure outcome. CONCLUSIONS: A subgroup of patients destined to have an excellent post-ATL outcome can be selected from MRI-negative TLE patients by using history and scalp-recorded interictal and ictal EEG data. The attributes of these patients are antecedent history of febrile seizures, strictly unilateral anterior IEDs, and concordant type 1 ictal EEG pattern.

Adolescent↗
PubMed1990

Survey of anti-human T-cell leukemia virus type I antibody in family members of patients with adult T-cell leukemia.

To evaluate the intrafamilial clustering of HTLV-I, we examined the sera or plasma of 296 healthy family members of patients with adult T-cell leukemia (ATL) for anti-HTLV-I antibodies. Of 296 subjects, 132 (44.6%) had anti-HTLV-I antibodies. Fifty-nine (41.0%) out of 144 males and 73 (48.0%) out of 152 females were seropositive. The positive rates of antibody to HTLV-I increased with age, especially between the 30-39 and the 40-49 age groups. Five out of 6 fathers, 3 out of 4 mothers, 31 (60.8%) out of 51 spouses, 40 (63.5%) out of 63 siblings and 46 (33.8%) out of 136 children of patients with ATL had anti-HTLV-I antibodies. Of 74 children with an ATL father, 14 (18.9%) were seropositive, while 32 (51.6%) out of 63 children with an ATL mother were seropositive. This difference was statistically significant (P less than 0.001). Of those children with an ATL father, 12 (26.1%) out of 46 whose mothers were HTLV-I carriers had antibodies to HTLV-I. In contrast, none of the 13 children whose mothers were not carriers were seropositive. These results supported the hypothesis that the mother-to-child transmission is one of the most important modes of HTLV-I transmission. In wives of male patients with ATL, the positive rate of antibody to HTLV-I was 65.6% (21/32), and in husbands of female patients, it was 52.6% (10/19). The high positive rate of antibody to HTLV-I not only in wives of male patients but also in husbands of female patients suggests that either HTLV-I is more frequently transmitted from wives to their husbands than we had originally expected, or that ATL may develop even in wives who acquire HTLV-I from their husbands after marriage.

Adult↗
PubMed1995

Detection of homing, proliferation, and infiltration sites of adult T cell leukemia cells in severe combined immunodeficiency mice using radiometric techniques.

To clarify the mechanism of in vivo proliferation of adult T cell leukemia (ATL) cells, we examined the organ distribution of ATL-43T cell line cells derived from original leukemic cells in severe combined immunodeficiency (SCID) mice using radiometric techniques. First, we injected 111In-oxine-labeled ATL-43T cells into SCID and CB17 mice. On day 6, significant accumulation of radioactivity was found in the spleen and thymus of SCID mice (33.3 +/- 9.4 and 10.0 +/- 3.6% injected dose/g of tissue [%ID/g], respectively) in comparison with that in CB17 mice (19.1 +/- 2.5 and 3.7 +/- 0.9%ID/g, respectively). Next, we injected radiolabeled anti-Tac monoclonal antibody (MoAb) recognizing human interleukin-2 receptor (IL-2R) alpha chain or isotype-matched control MoAb RPC5 in SCID mice bearing ATL-43T cells 4 weeks after cell inoculation. The amounts of radioactivity found in the spleen and thymus of SCID mice injected with 125I-labeled anti-Tac MoAb (22.5 +/- 6.9 and 22.8 +/- 9.6 %ID/g, respectively) were significantly higher than those in the corresponding organs of SCID mice injected with 125I-labeled RPC5 MoAb (12.0 +/- 5.1 and 7.5 +/- 4.6 %ID/g, respectively). Similar results were obtained with 111In-labeled anti-Tac MoAb. These results were consistent with the histological findings of SCID mice bearing ATL-43T cells, indicating that ATL-43T cells infiltrated preferentially into the lymphoid organs, such as the spleen and thymus, and proliferated there. Thus, the radiometric techniques employed in this study were very useful to evaluate the proliferation sites of ATL-43T cells in SCID mice. Furthermore, this murine model could give us an opportunity to test the feasibility of therapeutic application of radiolabeled anti-Tac MoAb.

Animals↗
PubMed2005

Tumor immunity against adult T-cell leukemia.

Human T-cell leukemia virus type-I (HTLV-I) causes adult T-cell leukemia (ATL) in a small population of infected individuals after a long incubation period. Although the process of clonal evolution of ATL cells may involve multiple steps, ATL cells from half of the ATL cases still retain the ability to express HTLV-I Tax, a key molecule of HTLV-I leukemogenesis. A recent finding of reactivation of Tax-specific cytotoxic T lymphocytes (CTL) in ATL patients after hematopoietic stem cell transplantation suggests the presence of Tax expression in vivo and potential contribution of the CTL to antitumor immunity. This is consistent with the results of a series of animal experiments indicating that Tax-specific CTL limit the growth of HTLV-I-infected cells in vivo, although the animal model mimics only an early phase of HTLV-I infection and leukemogenesis. Establishment of an insufficient HTLV-I-specific T-cell response and an increased viral load in orally HTLV-I-infected rats suggests that host HTLV-I-specific T-cell response at a primary HTLV-I infection can be a critical determinant of persistent HTLV-I levels thereafter. These findings indicate that Tax-targeted vaccines may be effective for prophylaxis of ATL in a high-risk group, and also for therapy of ATL in at least half the cases.

Animals↗
PubMed2005

Serum level of soluble CD30 correlates with the aggressiveness of adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) is a highly aggressive disease with poor prognosis. CD30(+) cells are frequently observed in lymph node cells and peripheral blood mononuclear cells of ATL patients. In order to elicit the role of CD30(+) cells in ATL development, we investigated expression of the membrane type of CD30 (mCD30) and the soluble form of CD30 (sCD30) on ATL cells. Both mCD30 and sCD30 are expressed on various numbers of ATL cells in vivo as well as cell lines such as MT-2, L540 and Karpas 299. The level of serum sCD30 in each clinical stage showed an elevated level in patients with acute type (mean +/- standard error; 545.2 +/- 18.6 U/mL) rather than with lymphoma type ATL (327.62 +/- 94.85 U/mL). In four patients whose sera were stored and examined longitudinally, the levels decreased following the response to chemotherapy but not in patients with chemotherapy resistance. Thus, our results imply that sCD30 levels may be another useful marker for the activity and aggressiveness of ATL.

Adult↗
PubMed1995

Language function after temporal lobectomy without stimulation mapping of cortical function.

We studied 95 patients who underwent standard anterior temporal lobectomy (ATL) without stimulation mapping of language areas, using neuropsychological parameters of language function preoperatively and 1 year postoperatively [Boston Naming Test and Verbal Fluency, and the Information, Comprehension, Arithmetic, Similarities, Digit Span, and Vocabulary subtests of the Wechsler Adult Intelligence Scale (WAIS)]. Verbal IQ (VIQ), Performance IQ (PIQ), Full-Scale IQ (FSIQ), and Verbal Deviation Quotient were also evaluated, as were parameters of memory function. All patients had hemisphere dominance for language assessed by an intracarotid amytal test. Fifty-three patients had a left dominant (LHDL) ATL with a mean extent of lateral resection of 4.8 cm, and 10 had a left ATL with right or mixed hemisphere dominance (RHDL, MDL). Thirty-two patients had a right nondominant ATL. Seizure outcome was 57 and 59% seizure-free for LHDH and right nondominant group, respectively, 1 year after operation. Comparison of preoperative scores showed the LHDL group to have significantly lower scores than the right nondominant group for several parameters of language function and memory. The group undergoing left dominant ATL showed no significant loss of language function postoperatively and actually showed gains in many parameters. Standard ATL without stimulation mapping of language areas and with conservative lateral resection is safe for long-term language function. In addition, evidence shows preexisting language dysfunction in patients undergoing left dominant ATL.

Adolescent↗
PubMed2006

Memory, emotional and vocational impairments before and after anterior temporal lobectomy for complex partial seizures.

PURPOSE: To assess the pre- and postsurgical frequency of memory, emotional, and vocational impairments in patients who underwent anterior temporal lobectomy (ATL), and to assess the relationship between emotional disturbance and memory abilities after ATL. METHODS: Retrospective analysis of data was performed on 90 patients with medically intractable complex partial seizures who underwent ATL between 1981 and 2003. Patients were evaluated an average of 5 months before surgery and 11.3 months after surgery. RESULTS: A moderate to high frequency of memory impairment (44.4%; verbal or nonverbal), emotional disturbance (38.9%) and unemployment (27.8%) existed in the same individuals both before and after surgery. There were small to moderate rates of new onset memory (18.9%), emotional (11.1%), and vocational (7.8%) difficulties after surgery often regardless of seizure control outcome. Patients who underwent left-ATL and had emotional disturbance after surgery had the lowest verbal memory test scores. CONCLUSIONS: Results highlight the importance of taking into account emotional status when assessing memory abilities after ATL. Results replicate the finding of moderate to high frequencies of memory impairment, emotional disturbance, and unemployment both before and after ATL. Results provide support for the rationale that cognitive, psychiatric and vocational interventions are indicated to mitigate the problems that exist before and persist after ATL.

Adolescent↗
PubMed1992

Treponemicidal activity of anti-treponemal lymphotoxins and their relation to circulating immune complexes and autolymphocytotoxins.

It was previously reported that spleen cells of rabbits infected with Treponema pallidum produced anti-treponemal lymphotoxins (ATL). This ability was distinctly disturbed when circulating immune complexes (CIC) and autolymphocytotoxins (AL) were present in the sera of cell donors. ATL liberated from cells of donors without CIC and AL displayed a marked ability to immobilize treponemes. The percentage of immobilized treponemes varied according to the type of cells used for ATL liberation and their density. The most active was ATL from T cells (density 4 x 10(8) ml-1) and the weakest was the one from B lymphocytes. In the presence of CIC in sera of cell donors the weakest ATL was from macrophages and in the presence of AL from T lymphocytes. When both factors (CIC and AL) were present ATL from T lymphocytes did not immobilize treponemes. This seems to suggest that the impairment of the cells' ability to produce ATL may facilitate the survival of treponemes in the host despite the presence of immunologically competent cells.

Animals↗
PubMed1995

Interleukin-4 inhibits the production of interleukin-1 by adult T-cell leukemia cells.

Freshly isolated leukemic cells from patients with adult T-cell leukemia (ATL) produce high levels of interleukin-1 (IL-1), which is believed to play an important role in neutrophilia, elevation of C-reactive protein, osteolytic bone lesions, hypercalcemia, and fever in ATL. However, relatively little is known regarding the regulatory mechanism of IL-1 production in ATL. Interleukin-4 (IL-4) affects the monocytes- and neoplastic cells-mediated cytokine production. In this study, we investigated the effect of IL-4 on IL-1 alpha and IL-1 beta production by ATL cells in vitro. IL-4 was found to markedly inhibit the release of IL-1 alpha and IL-1 beta into the conditioned medium in a dose-dependent manner. Northern blot analysis of steady-state IL-1 mRNA demonstrated that IL-4 treatment of ATL cells resulted in a reduction of IL-1 mRNA. These results support the notion that ATL cells spontaneously produce IL-1 alpha and IL-1 beta; however, such production can be inhibited by the immunomodulating agent, IL-4. IL-4 may play an important regulatory role in the production of IL-1 in ATL.

Aged↗
PubMed1995

Potential role of natural killer cells in controlling tumorigenesis by human T-cell leukemia viruses.

Human T-cell leukemia virus (HTLV) is the etiologic agent of adult T-cell leukemia (ATL), a malignancy of T lymphocytes that is characterized by a long latency period after virus exposure. Intraperitoneal inoculation of severe combined immunodeficient (SCID) mice with HTLV-transformed cell lines and ATL tumor cells was employed to investigate the tumorigenic potential of HTLV type I (HTLV-I)-infected cells. In contrast to inoculation of ATL (RV-ATL) cells into SCID mice, which resulted in the formation of lymphomas, inoculation of HTLV-I- and HTLV-II-transformed cell lines (SLB-I and JLB-II cells, respectively) did not result in tumor formation. Immunosuppression of SCID mice, either by whole-body irradiation or by treatment with an antiserum, anti-asialo GM1 (alpha-AGM1), which transiently abrogates natural killer cell activity in vivo, was necessary to establish the growth of tumors derived from HTLV-transformed cell lines. PCR and flow cytometric studies reveal that HTLV-I-transformed cells are eliminated from the peritoneal cavities of inoculated mice by 3 days postinoculation; in contrast, RV-ATL cells persist and are detected until the mice succumb to lymphoma development. The differing behaviors of HTLV-infected cell lines and ATL tumor cells in SCID mice suggest that ATL cells have a higher tumorigenic potential in vivo than do HTLV-infected cell lines because of their ability to evade natural killer cell-mediated cytolysis.

Animals↗
PubMed2004

Apoptosis induced by the histone deacetylase inhibitor FR901228 in human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells.

Inhibition of histone deacetylase (HDAC) activity induces growth arrest, differentiation, and, in certain cell types, apoptosis. FR901228, FK228, or depsipeptide, is an HDAC inhibitor effective in T-cell lymphomas. Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) and remains incurable. We examined whether FR901228 is effective for treatment of ATL by assessing its ability to induce apoptosis of HTLV-1-infected T-cell lines and primary leukemic cells from ATL patients. FR901228 induced apoptosis of Tax-expressing and -unexpressing HTLV-1-infected T-cell lines and selective apoptosis of primary ATL cells, especially those of patients with acute ATL. FR901228 also efficiently reduced the DNA binding of NF-kappaB and AP-1 in HTLV-1-infected T-cell lines and primary ATL cells and down-regulated the expression of Bcl-x(L) and cyclin D2, regulated by NF-kappaB. Although the viral protein Tax is an activator of NF-kappaB and AP-1, FR901228-induced apoptosis was not associated with reduced expression of Tax. In vivo use of FR901228 partly inhibited the growth of tumors of HTLV-1-infected T cells transplanted subcutaneously in SCID mice. Our results indicated that FR901228 could induce apoptosis of these cells and suppress the expression of NF-kappaB and AP-1 and suggest that FR901228 could be therapeutically effective in ATL.

Adult↗
PubMed2001

Selective A(2A) adenosine receptor activation reduces skin pressure ulcer formation and inflammation.

Activation of A(2A) adenosine receptors (A(2A)-AR) by ATL-146e (formerly DWH-146e) prevents inflammatory cell activation and adhesion. Recurrent ischemia-reperfusion (I/R) of the skin results in pressure ulcer formation, a major clinical problem. ATL-146e was evaluated in a novel reproducible rat model of pressure ulcer. A 9-cm(2) region of dorsal rat skin was cyclically compressed at 50 mmHg using a surgically implanted metal plate and an overlying magnet to generate reproducible tissue necrosis. Osmotic minipumps were implanted into 24 rats divided into four equal groups to infuse vehicle (control), ATL-146e (0.004 microg x kg(-1) x min(-1)), ATL-146e plus an equimolar concentration of A(2A) antagonist, ZM-241385, or ZM-241385 alone. Each group received 10 I/R cycles. In non-I/R-treated skin, ATL-146e has no effect on blood flow. I/R-treated skin of the ATL-146e group compared with the vehicle group had 65% less necrotic area, 31% less inhibition of average skin blood flow, and fewer extravasated leukocytes (23 +/- 3 vs. 49 +/- 6 per 500 microm(2)). These data suggest that ATL-146e, acting via an A(2A)-AR, reduces leukocyte infiltration and is a potent prophylactic for I/R injury in skin.

Animals↗
PubMed2005

Production of thymus and activation-regulated chemokine and macrophage-derived chemokine by CCR4+ adult T-cell leukemia cells.

PURPOSE: Adult T-cell leukemia/lymphoma (ATL) is a peripheral CD4(+)CD25(+) T-cell malignancy caused by human T-cell leukemia virus type I. The tumor cells frequently infiltrate in the skin, lymph nodes and other organs and especially form prominent cutaneous masses. Recently, ATL cells have been shown to express Th2 chemokine receptor CCR4. The aim of this study is to investigate the possibility that CCR4 ligands, thymus and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC), are produced by CCR4(+) ATL cells per se. EXPERIMENTAL DESIGN: CD4(+) or CD4(+)CD14(-) cells were purified from peripheral blood mononuclear cells of 11 ATL patients with cutaneous involvement and normal healthy volunteers. Tissue-infiltrating cells were isolated from skin tumors. The expression of chemokine receptors on these cells were analyzed by flow cytometry. The production of chemokines and cytokines by the neoplastic cells was assessed by ELISA and reverse transcription-PCR after cultivation for 96 hours in the presence or absence of anti-CD3/CD28 monoclonal antibodies. Finally, TARC and CCR4 expressions were examined by immunohistochemistry. RESULTS: ATL cells highly expressed CCR4 but did not necessarily exhibit the Th2 cytokine profile. The cells also produced TARC and MDC. The production level of MDC was higher in the skin tumor formation group than that in the nontumor group. Immunohistochemically, both CCR4 and TARC were expressed by the tumor cells in the lesional skin. CONCLUSIONS: ATL cells not only express CCR4 but also produce TARC and MDC. The skin tumor formation as well as the monoclonal integration of proviral DNA are the factors that are associated with the high production of Th2 chemokines by ATL cells.

Adult↗
PubMed1985

Functional and phenotypic studies of Japanese adult T cell leukemia cells.

The cell surface marker profile and functional analysis of peripheral blood lymphocytes from 11 Japanese adult T cell leukemia patients were studied. The phenotypic analysis of Japanese adult T cell leukemia (ATL) cells by a series of 13 monoclonal antibodies showed that all ATL cells are anti-T4 reactive but some differ in their expression of T3, T11, and T12 antigens. Thus, considerable phenotypic heterogeneity exists in these populations of leukemia cells. When analyzed in functional assays, ATL cells were suppressive when added to a pokeweed mitogen- (PWM) driven Ig synthesis system. However, the suppression mechanism seemed to be more complex than originally conceived. ATL cells examined in this study seem to function mainly as an inducer of suppressor cells, and as such, activate normal T8 precursors of suppressor cells rather than function as suppressor effector cells. In addition, no evidence was obtained to suggest that suppression of PWM-stimulated IgG synthesis was mediated by natural killer (NK) activity of ATL cells. Rather, ATL cells seem to be markedly deficient in NK activity. These studies suggest that the majority of ATL cells tested are representative of and seem to be the leukemic counterparts of the T4+ suppressor inducer subset.

Adult↗
PubMed2001

Autocrine antiapoptotic stimulation of cultured adult T-cell leukemia cells by overexpression of the chemokine I-309.

Adult T-cell leukemia (ATL) is an aggressive malignancy of CD4(+) T cells caused by the human T-cell leukemia virus type 1 (HTLV-1). The viral leukemogenesis is critically dependent on its oncoprotein Tax because the protein as well as the virus can immortalize primary human lymphocytes to permanent growth. As a transcriptional transactivator, Tax can stimulate the expression of distinct cellular genes. Alterations in the expression levels of unknown growth-relevant genes may contribute to the changed growth properties of Tax-immortalized and leukemic cells. To identify genes that are linked to Tax transformation and ATL leukemogenesis, this study systematically compared the gene expression of cultured cells from patients with acute ATL with that of stimulated peripheral blood T lymphocytes. Several overexpressed RNAs that encode signal transduction functions were identified. These include a dual-specific protein phosphatase (PAC1), an interferon-inducible factor (ISG15), a basic helix-loop-helix transcription factor (DEC-1), and the secreted antiapoptotic chemokine I-309. The ATL cell culture supernatants contained an antiapoptotic activity that could be specifically inhibited by antibodies directed against I-309. Inhibition of I-309 receptor (CCR8) signaling by pertussis toxin increased the apoptosis rate of ATL cell cultures in the presence and absence of external apoptotic stimuli. Both the I-309--specific antiapoptotic activity and the proapoptotic effect of inhibitors of I-309 signaling suggest the existence of an antiapoptotic autocrine loop in ATL cells. Thus, the overexpression of this chemokine may inhibit apoptosis in ATL cells and could substantially contribute to their growth. (Blood. 2001;98:1150-1159)

Apoptosis↗
PubMed2002

Mechanism of hypercalcemia in adult T-cell leukemia: overexpression of receptor activator of nuclear factor kappaB ligand on adult T-cell leukemia cells.

Hypercalcemia is one of the most frequent and serious complications in patients with adult T-cell leukemia (ATL) and is due to marked bone resorption by accumulation of osteoclasts (OCLs). Although several cytokines such as interleukin 1 and parathyroid hormone-related protein are thought to be involved in the development of high serum Ca(++) levels, its precise underlying mechanism remains unknown. This study analyzed the expression of various genes that are thought to regulate serum Ca(++) levels in ATL and showed that the overexpression of the receptor activator of nuclear factor kappaB (RANK) ligand gene correlated with hypercalcemia. ATL cells from patients with hypercalcemia, which highly expressed the transcripts of the RANK ligand (RANKL) gene, induced the differentiation of human hematopoietic precursor cells (HPCs) into OCLs in vitro in the presence of macrophage colony-stimulating factor (M-CSF). In contrast, ATL cells from patients without hypercalcemia did not induce such differentiation, suggesting that the induction of the differentiation correlated with the expression of the RANKL gene in ATL cells. Cell differentiation was suppressed by osteoprotegerin/Fc, an inhibitor of RANKL, indicating that such differentiation occurred through the RANK-RANKL pathway. In addition, direct contact between ATL cells and HPCs was essential for the differentiation, suggesting that not the soluble form but membrane-bound RANKL played a role in this process. These results strongly suggested that ATL cells induce the differentiation of HPCs to OCLs through RANKL expressed on their surface, in cooperation with M-CSF, and ultimately cause hypercalcemia.

Adult↗
PubMed2006

Inhibition of constitutively active Jak-Stat pathway suppresses cell growth of human T-cell leukemia virus type 1-infected T-cell lines and primary adult T-cell leukemia cells.

BACKGROUND: Human T-cell leukemia virus type 1 (HTLV-1), the etiologic agent for adult T-cell leukemia (ATL), induces cytokine-independent proliferation of T-cells, associated with the acquisition of constitutive activation of Janus kinases (Jak) and signal transducers and activators of transcription (Stat) proteins. Our purposes in this study were to determine whether activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells, and to explore mechanisms by which inhibition of Jak-Stat pathway kills ATL cells. RESULTS: Constitutive activation of Stat3 and Stat5 was observed in HTLV-1-infected T-cell lines and primary ATL cells, but not in HTLV-1-negative T-cell lines. Using AG490, a Jak-specific inhibitor, we demonstrated that the activation of Stat3 and Stat5 was mediated by the constitutive phosphorylation of Jak proteins. AG490 inhibited the growth of HTLV-1-infected T-cell lines and primary ATL cells by inducing G1 cell-cycle arrest mediated by altering the expression of cyclin D2, Cdk4, p53, p21, Pim-1 and c-Myc, and by apoptosis mediated by the reduced expression of c-IAP2, XIAP, survivin and Bcl-2. Importantly, AG490 did not inhibit the growth of normal peripheral blood mononuclear cells. CONCLUSION: Our results indicate that activation of Jak-Stat pathway is responsible for the proliferation and survival of ATL cells. Inhibition of this pathway may provide a new approach for the treatment of ATL.

Base Sequence↗
PubMed2003

Acute tumor lysis syndrome secondary to hydroxyurea in acute myeloid leukemia.

OBJECTIVE: To report 2 cases of acute tumor lysis syndrome (ATLS) associated with hydroxyurea treatment. CASE SUMMARY: A 79-year-old woman diagnosed with chronic lymphocytic leukemia presented with an acute blastic transformation. She was promptly hydrated, started on allopurinol, and treated with hydroxyurea. About 24 hours later, her biochemistry panel showed parameters consistent with ATLS when compared with pretreatment levels. The second case was a 76-year-old man newly diagnosed with acute myeloid leukemia presenting with high blast fraction. He was given appropriate hydration and allopurinol prophylaxis, and was started on high-dose hydroxyurea treatment. He became symptomatic after 12 hours and results of his blood work were consistent with ATLS. DISCUSSION: ATLS is a well-known metabolic disturbance that occurs after cell destruction of rapidly growing tumors. In standard doses, hydroxyurea leads to cell death in the S phase and is not thought to cause significant cell lysis. However, in large doses, it possibly acts by a different mechanism and had a direct cytolytic effect associated with ATLS in our patients. CONCLUSIONS: Although ATLS caused by hydroxyurea appears to be rare, patients at risk should be closely monitored for this complication. An objective causality assessment using the Naranjo probability scale revealed that the adverse drug reaction was probable between ATLS and hydroxyurea therapy in these 2 patients.

Aged↗