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PubMed1994

DNA aneuploidy of adult T-cell leukemia cells.

To clarify the biological characteristics of adult T-cell leukemia (ATL), immunophenotyping and DNA aneuploid analysis were performed in 72 ATL cases, using flow cytometric techniques. DNA aneuploidy was found in 45 cases (62.5%); the DNA index ranged from 1.03 to 2.16 (mean: 1.24). The incidence of aneuploidy in smoldering, chronic, acute, and lymphoma ATL subtypes was 20.0%, 46.6%, 76.3%, and 77.8%, respectively. The aneuploid patients had a greater tumor burden (adenopathy, hepatosplenomegaly, and leukocytosis with ATL cells), a higher level of serum LDH, and a higher incidence of hypercalcemia, compared with the diploid group. Further, unusual aberrant immunophenotypes were identified predominantly in the aneuploid group. Patients with aneuploidy had a 7.6 month median survival time (MST) with a 2 year survival rate of 24.6%, significantly worse than in the patients with diploidy, whose MST was 25.4 months with a 2 year survival of 60.1%. In some aneuploid patients, the disease often progresses from a static to an aggressive form. Thus, the determination of aneuploidy and unusual immunophenotype should be useful for detecting clinical behavior and for monitoring ATL patients, particularly in regard to such progression.

Adult↗
PubMed1991

Cytogenetic implication in adult T-cell leukemia. A hypothesis of leukemogenesis.

The close association between adult T-cell leukemia (ATL) and human T-cell leukemia virus type I (HTLV-I) has been established. Nevertheless, the mechanism of progression of ATL by HTLV-I infection is still uncertain, because the virus contains no typical oncogene and no significant expression of the viral RNA has been generally found. I propose a model of leukemogenic process in ATL based on our cytogenetic data and molecular results in the literature. It seems that the rearrangement of some proto-oncogene and alpha-chain gene of the T-cell antigen receptor (TCR-alpha) is necessary for the development to overt ATL. A deficiency in the rearrangement of proto-oncogene to TCR-alpha may result in only a minor proliferation of abnormal lymphocytes and remain in the preleukemic state of ATL or in the HTLV-I carrier state.

Adult↗
PubMed2004

Outcomes of advanced trauma life support training: questioning the role of observer.

Trauma is the leading cause of mortality in young adults in the United Kingdom. Many such deaths are preventable if patients are treated effectively. Delay in providing care by experienced, trained staff is seen as a major factor in unsatisfactory trauma management. In order to reduce the number of deaths, the Advanced Trauma Life Support (ATLS) system has been recommended for use in the management of patients with major injuries. However, there is little evidence to support the participation of nurses in the ATLS system. The aim of this study was to investigate the influence of ATLS training on the performance of nurses in Accident and Emergency, taking account of experience and intuition. Results suggest that the Trauma Nursing Core Course and the Advanced Trauma Nursing Course have a positive influence on nurses' performance. Experienced staff who had received full, participative ATLS training demonstrated an improved understanding of the trauma situation resulting in rapid and accurate decision-making. However, attending the ATLS course as an observer appears to have minimal effect on a nurse's performance and such non-participant training should no longer be considered as equivalent to participant training.

Attitude of Health Personnel↗
PubMed2004

Methylenetetrahydrofolate reductase genotype does not play a role in adult T-cell leukemia/lymphoma pathogenesis among human T-lymphotrophic virus type 1 carriers.

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia/lymphoma (ATL). However, the incidence of ATL is low among HTLV-1 carriers suggesting additional mechanisms are involved in the progression of the disease. A recent study found that polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene influence the susceptibility to malignant lymphoma. We have analyzed the MTHFR genotype in 81 HTLV-1 carriers and 87 ATL patients. No statistically significant associations were found between MTHFR genotype and development of ATL. These data suggest that genetic polymorphisms in the MTHFR locus do not play a role in ATL pathogenesis among HTLV-1 carriers.

Carrier State↗
PubMed2005

Determining empirically based self-reported cognitive change: development of reliable change indices and standardized regression-based change norms for the multiple abilities self-report questionnaire in an epilepsy sample.

PURPOSE: Reliable change indices (RCIs) and standardized regression-based (SRB) change score norms were calculated for a measure of self-reported cognitive function, the Multiple Abilities Self-Report Questionnaire (MASQ), in patients with complex partial seizures. Establishment of such standardized change scores could be useful in determining the magnitude and direction of self-appraised cognitive change after epilepsy surgery or other treatment interventions. The primary study objective was to calculate RCI and SRB values for the MASQ. A secondary objective was to report SRB change scores in patients who had undergone anterior temporal lobectomy (ATL) and to assess relationships between self-reported cognitive change, seizure outcome, objective memory test performance, and mood. METHODS: The MASQ was administered to 36 patients with complex partial seizures on two occasions (mean test-retest interval, 6 months). This group did not have major psychopathology and were on stable antiepileptic drugs. RCI and SRB change scores were calculated. Adjustments for baseline ratings, age, education, gender, age at seizure onset, and seizure duration were made with the SRB method. A confidence interval cutoff score (90% level) was calculated for the five MASQ cognitive domains (Language, Visual Perception, Verbal Memory, Visual-Spatial Memory, Attention/Concentration). MASQ SRB scores were computed for a second sample of 50 patients who had undergone ATL. RESULTS: Test-retest reliabilities for the MASQ domains ranged from a low of 0.63 (Attention/Concentration) to a high of 0.87 (total score). Baseline MASQ score was the single largest contributor to the regression equations. Left and right ATL groups demonstrated similar magnitudes of self-reported cognitive change across all five MASQ domains. Individual base rate change distributions were similar across four of the five domains. with a higher proportion of right ATL patients reporting worsening attention function. Both postoperative mood and SRB-based verbal memory outcome were significantly correlated to self-reported cognitive change in the patients who had undergone ATL. CONCLUSIONS: SRB methodology provides a standardized technique with which to establish patient perception of cognitive change and may be of use when examining change across individual- and group-level ratings of cognitive functioning in clinical and research settings. These techniques also provide a common metric for direct comparison between subjective self-report ratings of cognitive function and objective cognitive test instruments.

Adolescent↗
PubMed1997

Frequent expression of interleukin-9 mRNA and infrequent involvement of interleukin-9 in proliferation of primary adult T-cell leukemia cells and HTLV-I infected T-cell lines.

To examine the possibility that interleukin-9 (IL-9) may be involved in oncogenesis and the proliferation of adult T-cell leukemia (ATL) cells, we examined the expression of IL-9 mRNA and growth response to IL-9 in five human T-lymphotropic virus type-I (HTLV-I) infected T-cell lines and in primary leukemia cells in peripheral blood from eight patients with ATL (four acute ATL and four chronic). Four out of five cell lines expressed IL-9 mRNA not correlated with Tax expression. Primary ATL cells from all patients also expressed IL-9 mRNA not correlated with the clinical forms. Recombinant IL-9 showed growth enhancing activity in only one out of five cell lines and one out of eight patients' primary leukemic cells. These results suggest the infrequent involvement of IL-9 in the proliferation of ATL cells, both primary tumor cells and HTLV-I infected T-cell lines.

Adult↗
PubMed1999

Correlation of telomerase activity with development and progression of adult T-cell leukemia.

Telomerase is an enzyme that adds hexameric TTAGGG nucleotide repeats to the ends of vertebrate chromosomal DNAs (i.e. telomeres) to compensate for losses that occur with each round of DNA replication. Telomerase activity, demonstrable in most human tumors, enables them to maintain telomere stability. Peripheral blood mononuclear cells were sampled from 57 patients seropositive for human T-lymphotropic virus type I (HTLV-I), including 24 asymptomatic viral carriers, ten smoldering type, five chronic type, and 18 acute type adult T-cell leukemia (ATL). Telomerase activity was determined in samples using a modified telomeric repeat amplification protocol. We semiquantitatively determined telomerase activity by serial dilution of each sample. All of 23 samples from acute and chronic type ATL patients were positive, seven of ten (70%) smoldering type patients and seven of 24 (29.2%) asymptomatic viral carriers were positive. Disease progression from asymptomatic viral carrier to acute type correlated with telomerase activity. Two samples from chronic type ATL patients with relatively high telomerase activity progressed to the acute type within 1 month. Serum lactate dehydrogenase level also correlated with telomerase activity. These results indicate that reactivation of telomerase activity is a key event in development and progression of ATL, and telomerase could be a useful marker for predicting the course of disease. Accordingly, ATL could be a good candidate disease for trials of telomerase inhibitors, as novel anticancer drugs.

Adult↗
PubMed2004

Memory for faces dissociates from memory for location following anterior temporal lobectomy.

It has been suggested that the right and left mesial temporal lobes are specialized for processing different types of information for long-term memory (LTM). Although findings have been consistent in regard to the dominant role of the left mesial temporal lobe (MTL) in verbal memory, the role of the right MTL in non-verbal memory remains debatable. Given the existence of two cortical pathways specialized for processing different types of visuospatial information, we examined whether memory processing for these two types of information might also be differentially localized. The effect of unilateral anterior temporal lobectomy (ATL) was compared for memory for unfamiliar faces and a novel sequence of spatial locations in 86 ATL patients (left ATL (LATL) = 35; right ATL (RATL) = 51) pre- and post-surgery to examine the contributions of right and left MTL structures to LTM for pattern and spatial information. Memory for spatial location was not related to side of ATL or time of testing. On the facial memory task, RATL patients showed impairments relative to LATL patients prior to surgery, which became magnified after surgery. These results extend the proposed dissociation between an occipitotemporal and an occipitoparietal pathway for processing visuospatial information by demonstrating dissociations in LTM systems for these two types of information. Lesions in the right MTL, adjacent to the cortical structures believed to be specialized for facial recognition, specifically impair the memory encoding of new faces, but not spatial locations.

Adult↗
PubMed1979

Advanced Trauma Life Support laboratory: pilot implementation and evaluation.

Selected invasive diagnostic and therapeutic techniques were taught to emergency physicians through modular Advanced Trauma Life Support (ATLS) animal laboratory courses presented in the fall of 1977. Thirty-seven emergency physicians participated in the four pilot ATLS laboratories in which the average trainee:animal:instructor ratio was 2:1:0.75. The animals consisted of 15 large baboons and five large rhesus monkeys. Cost accounting on these pilot ATLS courses revealed that the total program cost was $15,581.86, for an average of $3,895.46 per trauma laboratory course and $421.13 per emergency physician trained. The ATLS concept is ready for development into a nationally-standarized ATLS series.

Animals↗
PubMed2003

A novel rat lipoxin A4 receptor that is conserved in structure and function.

1. Lipoxin (LX) A(4) and aspirin-triggered-LX (ATL) are endogenous lipid-derived mediators that regulate leukocyte trafficking via specific LXA(4) receptors (ALX), and are involved in endogenous anti-inflammation and resolution. Both LXA(4) and ATL are produced by rat tissues in vitro as well as in vivo. In rats, LXA(4) and ATL exhibit potent physiological and pathophysiological roles. Thus, we set out to determine whether ALX is expressed in rat tissues and its potential role in modulating leukocyte trafficking with LXA(4) and ATL. 2. In rats, a stable analog of ATL, when given intravenously with two consecutive doses at approximately 60 microg kg(-1) each injection, significantly inhibited neutrophil infiltration (approximately 43%) and protein extravasation (approximately 42%) in a casein-induced peritonitis. 3. The rat orthologue of ALX was cloned from peripheral blood leukocytes encoding a putative G protein-coupled receptor (GPCR). It gave approximately 74 and approximately 84% homology, respectively to the deduced amino-acid sequences of the human and mouse ALX. 4. Tissue distribution analysis by RNase protection revealed that this rat receptor is expressed in tissues/cells, where LXA(4) displays physiological and pathophysiological roles, namely, lung, kidney and leukocytes. 5. The rat orthologue of ALX gave specific radioligand binding with [(3)H]LXA(4) and [(125)-Tyr]-annexin 1-derived peptide with apparent K(d) values of 5 and 820 nM, respectively, that are at levels comparable to those of the human ALX. 6. Activation of rat ALX inhibited tumor necrosis factor alpha-mediated nuclear factor kappaB activity in a ligand-dependent manner utilizing a luciferase reporter gene system. 7. Together, these results are the first demonstration of a rat ALX that is conserved in both structure and function suggesting that ALX plays key roles in regulating effector immune responses from murine to human species.

Amino Acid Sequence↗
PubMed2003

Evidence that 5-lipoxygenase and acetylated cyclooxygenase 2-derived eicosanoids regulate leukocyte-endothelial adherence in response to aspirin.

(1) Unlike other nonsteroidal anti-inflammatory drugs that inhibit formation of cyclooxygenase (COX)-dependent eicosanoids, acetylation of COX-2 by aspirin switches eicosanoid biosynthesis from prostaglandin E(2) (PGE(2)) to 15-epi-lipoxin A(4) (15-epi-LXA(4) or aspirin-triggered lipoxin, ATL). ATL formation by activated leukocytes (PMN) requires the intervention of 5-lipoxygenase (5-LOX), an enzyme that is involved in leukotriene B(4) (LTB(4)) formation. (2) In the present study, we have examined the role of acetylated COX-2 and 5-LOX in modulating antiadhesive effects of aspirin on adhesion of PMN to endotoxin (LPS)-primed human umbilical endothelial cells (HUVEC). (3) Treating PMN/HUVEC cocultures with aspirin resulted in a concentration-dependent inhibition of cell-to-cell adhesion induced by LPS. Treating HUVEC with selective COX-2 inhibitors, celecoxib and rofecoxib, caused an approximately 70% reversion of antiadhesive effect of aspirin. In contrast, inhibition of neutrophil's 5-LOX pathway with 1 micro M ZD2138, a selective 5-LOX inhibitor, 1 micro M BAY-X-1005, a FLAP inhibitor, or 100 micro M licofelone, a dual COX/5-LOX inhibitor, did not affect antiadhesive properties of aspirin. (4) Exposure to celecoxib (100 micro M) or rofecoxib (10 micro M) completely suppressed ATL formation caused by aspirin without affecting LTB(4) levels. ZD2138, licofelone and BAY-X-1005 inhibited ATL formation as well as LTB(4) generation. (5) Treatment with LXA(4) reduced PMN adhesion to HUVEC and counteracted the proadhesive effect of celecoxib. In contrast, exposure to Boc-1, an LXA(4) antagonist, counteracts the antiadhesive activities of aspirin. Exposure to U75302, an LTB(4) receptor antagonist, enhances the antiadesive effect of aspirin. (6) Reversal of antiadhesive activities of aspirin by celecoxib was associated with increased expression of LFA-1 on PMN and E-selectin on HUVEC. Addition of LXA(4), ZD2138 and U75302 inhibited these changes. (7) The present results support the notion that inhibition of ATL formation is mechanistically linked to the reversal of the antiadhesive activity of aspirin caused by selective COX-1 inhibitors and suggests that the LTB(4)/ATL balance modulates pro- and antiadhesive activity of nonsteroidal anti-inflammatory drugs at the leukocyte-endothelial cell interface.

Acetates↗
PubMed2004

Lipoxins and novel 15-epi-lipoxin analogs display potent anti-inflammatory actions after oral administration.

1. Lipoxins (LX) and aspirin-triggered 15-epi-lipoxins (ATL) exert potent anti-inflammatory actions. In the present study, we determined the anti-inflammatory efficacy of endogenous LXA(4) and LXB(4), the stable ATL analog ATLa2, and a series of novel 3-oxa-ATL analogs (ZK-996, ZK-990, ZK-994, and ZK-142) after intravenous, oral, and topical administration in mice. 2. LXA(4), LXB(4), ATLa2, and ZK-994 were orally active, exhibiting potent systemic inhibition of zymosan A-induced peritonitis at very low doses (50 ng kg(-1)-50 microg kg(-1)). 3. Intravenous ZK-994 and ZK-142 (500 microg kg(-1)) potently attenuated hind limb ischemia/reperfusion-induced lung injury, with 32+/-12 and 53+/-5% inhibition (P<0.05), respectively, of neutrophil accumulation in lungs. The same dose of ATLa2 had no significant protective action. 4. Topical application of ATLa2, ZK-994, and ZK-142 ( approximately 20 microg cm(-2)) prevented vascular leakage and neutrophil infiltration in LTB(4)/PGE(2)-stimulated ear skin inflammation. While ATLa2 and ZK-142 displayed approximately equal anti-inflammatory efficacy in this model, ZK-994 displayed a slower onset of action. 5. In summary, native LXA(4) and LXB(4), and analogs ATLa2, ZK-142, and ZK-994 retain broad anti-inflammatory effects after intravenous, oral, and topical administration. The 3-oxa-ATL analogs, which have enhanced metabolic and chemical stability and a superior pharmacokinetic profile, provide new opportunities to explore the actions and therapeutic potential for LX and ATL.

Administration, Oral↗
PubMed2006

Oncolytic activity of vesicular stomatitis virus in primary adult T-cell leukemia.

Treatments for hematological malignancies have improved considerably over the past decade, but the growing therapeutic arsenal has not benefited adult T-cell leukemia (ATL) patients. Oncolytic viruses such as vesicular stomatitis virus (VSV) have recently emerged as a potential treatment of solid tumors and leukemias in vitro and in vivo. In the current study, we investigated the ability of VSV to lyse primary human T-lymphotropic virus type 1 (HTLV-1)-infected T-lymphocytes from patients with ATL. Ex vivo primary ATL cells were permissive for VSV and underwent rapid oncolysis in a time-dependent manner. Importantly, VSV infection showed neither viral replication nor oncolysis in HTLV-1-infected, nonleukemic cells from patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and in naive CD4(+) T-lymphocytes from normal individuals or in ex vivo cell samples from patients with chronic lymphocytic leukemia (CLL). Interestingly, activation of primary CD4(+) T-lymphocytes with anti-CD3/CD28 monoclonal antibody, and specifically with anti-CD3, was sufficient to induce limited viral replication and oncolysis. However, at a similar level of T-cell activation, VSV replication was increased fourfold in ATL cells compared to activated CD4(+) T-lymphocytes, emphasizing the concept that VSV targets genetic defects unique to tumor cells to facilitate its replication. In conclusion, our findings provide the first essential information for the development of a VSV-based treatment for ATL.

Animals↗
PubMed1999

Discrepant expression of membrane and soluble isoforms of Fas (CD95/APO-1) in adult T-cell leukaemia: soluble Fas isoform is an independent risk factor for prognosis.

The Fas signalling system probably plays a critical role in the natural and chemotherapeutic cell death machinery, suggesting that aberrant Fas expression is involved in growth control of tumours. The membrane isoform (mFas) is a 45 kD cell surface protein containing a single transmembrane region, and induces apoptosis in normal or tumour cells, whereas the soluble isoform (sFas) lacks the transmembrane domain due to alternative splicing of the transcript and is thought to block Fas-mediated apoptosis. To clarify the clinical roles of expression of these two Fas isoforms in adult T-cell leukaemia (ATL), we investigated the levels of the Fas isoforms in 81 patients with ATL. The expression patterns of the Fas isoforms were heterogenous, and there was no significant correlation between mFas and sFas levels: 10/81 cases were negative for mFas and had high serum sFas levels, whereas the remaining 71 cases were positive for mFas and had various levels of expression of the two Fas isoforms. Irrespective of the status of mFas expression in leukaemic cells, the mRNAs encoding these isoforms were always detectable, indicating the potential for protein translation. Although mFas expressed on freshly isolated ATL cells could iduce apoptosis in vitro, positive versus negative mFas status was not associated with any clinical aspects of ATL, whereas the sFas level was strongly correlated with clinical parameters such as serum LDH activity, tumour burden, serum soluble IL-2R level, hypercalcaemia and prognosis. These results suggest that the ratio of Fas isoforms varies, and high expression of the sFas protein and message reflects the malignant behaviour of ATL and is an independent risk factor for the prognosis.

Female↗
PubMed1996

Advanced trauma life support.

From a family tragedy 20 years ago, ATLS has truly become an international trauma care program. Its success is demonstrated not only in the large number of physicians that have been trained, but also in the appearance of a number of affiliated courses with a similar structure, aimed at training medical, nursing, civilian and military personnel in how to deal with trauma in a variety of settings. A great deal of time and money has been spent on reaching this point and ATLS has undoubtedly had a profound effect on members of the medical profession worldwide. Few would doubt that ATLS has contributed to the overall improvement in the care of the victims of trauma and saved lives; yet we still lack the evidence to support what many of us feel so strongly about. We are now faced with the next major stage in the development of ATLS, namely to provide the evidence for the efficacy of this in an acceptable scientific manner. It is a challenge we should accept with the same enthusiasm that originally embraced ATLS, and where better to meet this challenge than within the countries of Europe?

Humans↗
PubMed2001

Adult T-cell lymphoma involving the leptomeninges associated with a spinal cord schwannoma.

Adult T-cell lymphoma (ATL-L) developing initially in the meninges is rare. An autopsy case of ATL-L with an acute onset of meningitis and generalized lymphadenopathy in association with a cervical cord schwannoma is reported here. A 78-year-old woman with sensori-motor weakness of both arms over a 1-year period, developed febrile episodes and drowsiness with neck stiffness. Lumbar puncture revealed an increased protein content (161 mg/dL) and increased cell count (463/3) consisting of 99% of lymphocytes which contained atypical lymphocytes with multilobulated nuclei ('flower cells'), which are characteristic of ATL-L. Viral titers were positive only for HTLV-I antibodies (serum X 640: CSF X 16). Biopsy of an enlarged retroperitoneal lymph node revealed malignant lymphoma of the T-cell type. Brain MRI was negative, whereas an intradural extramedullary mass was found at the C4 level. With a diagnosis of ATL-L stage IV, chemotherapy was commenced, which was effective in reducing the generalized lymphadenopathy as well as the cervical mass and restoring the CSF findings to normality. The cervical cord mass was verified to be a solitary schwannoma, and ATL-L involvement was found not only in the leptomeninges, but also within the cervical cord schwannoma.

Aged↗
PubMed2003

Seizure control and cognitive outcome after temporal lobectomy: a comparison of classic Ammon's horn sclerosis, atypical mesial temporal sclerosis, and tumoral pathologies.

PURPOSE: Neuropathologic examination of resected tissue after anterior temporal lobectomy (ATL) for treatment of complex partial seizures revealed several distinct histologic substrates. Our study examined the relation between neuropathology, seizure control, and cognition in ATL patients and described preliminary profiles to aid in the prediction of outcome. METHODS: Of the 149 patients who underwent ATL from 1980 to 1999, long-term follow-up was available for 145. Specimens from 124 of the 145 patients had histologic findings consistent with one of three diagnoses: classic Ammon's horn sclerosis (cAHS; n = 75), atypical mesial sclerosis (Atypical; n = 21), or low-grade tumor (Tumor; n = 28). The other 20 patients had diverse pathologies that were insufficient for analysis. ATL patients underwent a complete preoperative and 68 underwent a postoperative neuropsychological evaluation. RESULTS: Of the 145 patients, 84% of cAHS, 57% of Tumor, and 29% of Atypical patients had a > or =95% reduction in seizure frequency. Neuropsychological testing suggested that cAHS patients demonstrate more generalized preoperative cognitive impairment than do the Atypical or Tumor patients. The Atypical group recalled significantly less nonverbal material after surgery than did the cAHS or Tumor groups. Stratification by both pathology and surgery side revealed that the right Atypical patients declined more on information processing and set shifting. CONCLUSIONS: Patients with cAHS or Tumor demonstrated better seizure control and fewer declines in cognitive functioning after ATL than did the Atypical patients, highlighting the need to investigate this group as a distinct entity.

Adolescent↗
PubMed2000

Human T-lymphotropic virus type 1 infection.

Human T-cell lymphotropic virus type-1 (HTLV-1) is aetiologically associated with adult T-cell leukaemia/lymphoma (ATL). HTLV-1 infection can also lead to various non-malignant diseases, for example, HTLV-1 associated myelopathy/tropical spastic paraparesis and HTLV-1 uveitis. HTLV-1 is endemic in southern Japan and the Caribbean. HTLV-1 infection is mainly transmitted by either breast-feeding, sexual intercourse or blood transfusions. Primary prevention of HTLV-1 in endemic areas by screening of blood and by refraining from breast-feeding have been successful. The incidence of ATL is rather low among HTLV-1 carriers (<5%). The precise mechanism of development of ATL remains unknown. It is a multiple-step process which does not require viral expression in the later stages of leukaemogenesis. Many samples have mutations of the tumour suppressor genes, p53 and/or p16(INK4A). Four subtypes of ATL have been identified, each having distinctive clinical features. Monoclonal integration of HTLV-1 proviral DNA into tumour cells is found in each of the subtypes. At present, no effective therapy for ATL exists.

Blood Cells↗