scholarly journals Variegated RHOA mutations in adult T-cell leukemia/lymphoma

Blood ◽  
2016 ◽  
Vol 127 (5) ◽  
pp. 596-604 ◽  
Author(s):  
Yasunobu Nagata ◽  
Kenji Kontani ◽  
Terukazu Enami ◽  
Keisuke Kataoka ◽  
Ryohei Ishii ◽  
...  

Key Points RHOA mutations are common in ATLL and show a unique distribution compared with other T-cell lymphomas. Depending on patients, functionally distinct RHOA mutations are clonally selected and involved in the pathogenesis of ATLL.

Blood ◽  
2013 ◽  
Vol 121 (21) ◽  
pp. 4340-4347 ◽  
Author(s):  
Makoto Ishihara ◽  
Natsumi Araya ◽  
Tomoo Sato ◽  
Ayako Tatsuguchi ◽  
Naomi Saichi ◽  
...  

Key Points Proteome-wide analysis of HTLV-1–infected T cells identified 17 biomarker proteins for the diagnosis of ATL or HAM/TSP patients.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 5026-5026
Author(s):  
Neeraj Agnihotri ◽  
Yiwu Huang ◽  
Perry Gerard

Abstract Abstract 5026 Introduction Adult T cell leukemia/lymphoma(ATL) is a distinct peripheral T cell lymphocytic malignancy associated with a retrovirus Human T cell Lymphotropic Virus type I(HTLV I). Patients with aggressive ATL generally have a poor prognosis. Positron Emission Tomography (PET) scan is highly sensitive and specific in the imaging of B-cell lymphomas, however the use in T- cell lymphomas is less defined. PET scan images from the skull base to mid thigh only, are generally obtained for staging of these lymphomas. We demonstrate two cases in which inclusion of below the knee areas on the PET scan lead to detection of impending fractures and timely intervention preventing morbidity and delay in treatment. Case report Our first patient was a 45 year old African American female who presented to us with chief complaints of generalized lethargy and significant weight loss. Labs revealed hypercalcemia of 15 mg/dl which was treated emergently. CT scan of the chest abdomen and pelvis revealed lymphadenopathy in the subcarinal, bilateral hilar and posterior mediastinal areas and evidence of sclerotic foci in the pelvis and bilateral femoral heads. Bone marrow biopsy was done which showed peripheral T cell lymphoma with CD 3, CD 5 positive, CD 20 negative and CD 43 positive. In addition HTLV I antibody was positive by western blot analysis which confirmed the diagnosis of Adult T cell leukemia/lymphoma. Our second patient was a 32 year old Caribbean male who presented with diffuse cervical lymphadenopathy and weight loss over one month duration. Labs revealed hypercalcemia of 12.5 mg/dl, which was treated. Biopsy of the right cervical lymph node revealed a diagnosis of peripheral T cell lymphoma with CD 2, CD 3, CD 4 and CD 5 positive. HTLV I antibody was found positive confirming the diagnosis of Adult T cell leukemia/lymphoma. Bone marrow was also involved. In both of these patients, we obtained a whole body PET scan for staging with special instructions to obtain images from the skull to both feet, keeping in mind the presentation with hypercalcemia and the propensity of this particular malignancy to involve the bones. PET scan in the first patient revealed increased uptake in lymph node areas mentioned above. Interestingly, there were multiple foci of uptake in the lower extremities from pelvis to feet bilaterally with multiple lytic areas in cortical and medullary areas with an area of cortical disruption in right tibial area indicating an impending fracture. PET scan in the second patient revealed adenopathy in neck, chest, abdomen, osseous lesions in the sternum, vertebrae, several cortical lytic lesion in bilateral lower extremities and a lesion in right mid tibia extending into medullary space indicating an impending fracture. Based on PET scan results of below the knee impending fractures in both the patients, orthopedic evaluation was obtained prior to instituting chemotherapy. Patients were suggested to limit weight bearing on the affected side, thus preventing increased morbidity and delay in institution of chemotherapy from the possible fractures. Conclusions Limited data available on the use of PET in peripheral T cell lymphomas suggests that it is very sensitive and highly specific at diagnosing nodal and non cutaneous extra-nodal disease, but not very sensitive for cutaneous lesions. Skull base to proximal thigh imaging is generally recommended to survey the body in search for areas of abnormal tracer accumulation for most tumor types including lymphomas. In addition, asymptomatic patients are unlikely to have areas below mid thigh included in PET imaging. Our experience with using whole body PET imaging in these two cases of adult T cell leukemia/lymphoma demonstrates the increased diagnostic value of using whole body PET scan even in asymptomatic patients with this lymphoma. Both the patients had unstable bone lesions which would have been missed on a routine skull base to mid thigh PET scan with increased likelihood of a fracture. Therefore, skull base to feet whole body PET scan should be used for more accurate staging and assessment and to prevent increased morbidity and delay in treatment of these aggressive lymphomas. Disclosures No relevant conflicts of interest to declare.


Oncogene ◽  
2004 ◽  
Vol 24 (3) ◽  
pp. 419-430 ◽  
Author(s):  
Rihab Nasr ◽  
Marwan E El-Sabban ◽  
José-Antonio Karam ◽  
Ghassan Dbaibo ◽  
Youmna Kfoury ◽  
...  

Blood ◽  
2013 ◽  
Vol 121 (11) ◽  
pp. 2029-2037 ◽  
Author(s):  
Jing Chen ◽  
Cynthia A. Pise-Masison ◽  
Joanna H. Shih ◽  
John C. Morris ◽  
John E. Janik ◽  
...  

Key Points Markedly additive antitumor activity with the combination of a selective survivin suppressant (YM155) and alemtuzumab in adult T-cell leukemia.


Blood ◽  
2013 ◽  
Vol 121 (25) ◽  
pp. 5045-5054 ◽  
Author(s):  
Marcia Bellon ◽  
Nga Ling Ko ◽  
Min-Jung Lee ◽  
Yuan Yao ◽  
Thomas A. Waldmann ◽  
...  

Key Points Profiling of the Wnt/β-catenin pathway reveals overexpression of Wnt5a, LEF-1 and TCF-1 in ATL patient cells. ATL cells overexpress Wnt5a, which enhances osteoclastogenesis and may contribute to the osteolytic bone lesions and hypercalcemia.


Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. 2072-2080 ◽  
Author(s):  
Hiba El Hajj ◽  
Bariaa Khalil ◽  
Botheina Ghandour ◽  
Rihab Nasr ◽  
Sharif Shahine ◽  
...  

Key Points The synthetic retinoid ST1926 induces apoptosis of ATL cells and prolongs survival of ATL mice. At the molecular level, ST1926 causes early DNA damage, upregulates p53, and downregulates Tax expression.


Blood ◽  
2015 ◽  
Vol 125 (23) ◽  
pp. 3527-3535 ◽  
Author(s):  
Yuya Nagai ◽  
Masahiro Kawahara ◽  
Masakatsu Hishizawa ◽  
Yayoi Shimazu ◽  
Noriko Sugino ◽  
...  

Key Points ATL clones are preserved in a rare CD4+CD45RA+ TSCM population. ATL-TSCM cells unidirectionally produce conventional CD45RO+ ATL cells and show a high potency of repopulating identical ATL clones in vivo.


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