Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic lymphocytic leukemia (cll) is the most common adult leukemia in the Western world. Unfortunately, affected patients are often immunosuppressed and at increased risk of infection and secondary malignancy. Previous meta-analysis has found that patients with cll have a risk of melanoma that is increased by a factor of 4 compared with the general population. Recent advances in the understanding of the PD receptor pathway have led to immunotherapies that target cancer cells. The use of PD-1 inhibitors is now considered first-line treatment for BRAF wild-type metastatic melanoma. Interestingly, early preclinical data suggest that inhibition of that pathway could also be used in the treatment of cll; however, recent clinical data did not support the effectiveness of that approach. In this case series, we highlight 2 cases in which patients with cll and concurrent malignant melanoma underwent treatment with PD-1 inhibitors and were found to experience reductions in their white blood cell counts without improvement in their hemoglobin. Those cases further illustrate that treatment of cll with PD-1 inhibitors is ineffective.
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PMID:PD-1 inhibition in malignant melanoma and lack of clinical response in chronic lymphocytic leukemia in the same patients: a case series. 3266 28

Breast tissue can be the host of not only many benign and malignant tumors but can also be a metastatic site for various tumors such as leukemia, lung cancer, and melanoma. This report describes an unusual case of a 43-year-old female who presented with a new palpable breast lump and several similar extramammary lumps on her skin. A melanoma panel, consisting of S100, HMB45, and Melan-A stains, was included in the pathology evaluation due to diagnostic suspicion of the radiologist and revealed metastatic melanoma. This case highlights the importance of detailed history and relevant physical exam as well as clinical and imaging correlation. It serves as a reminder to radiologists to include metastatic melanoma in the differential of suspicious subcutaneous breast masses, especially in patients with multiple subcutaneous lumps in the body or abnormal skin findings.
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PMID:Metastatic melanoma presenting as a breast mass - role of radiologist as a clinician. 3291 79

Metastatic melanoma remains an incurable disease for many patients due to the limited success of targeted and immunotherapies. BRAF and MEK inhibitors reduce metastatic burden for patients with melanomas harboring BRAF mutations; however, most eventually relapse due to acquired resistance. Here, we demonstrate that ABL1/2 kinase activities and/or expression are potentiated in cell lines and patient samples following resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK/ERK/MYC signaling. Silencing/inhibiting ABL1/2 blocks pathway reactivation, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively active ABL1/2 is sufficient to promote resistance. Significantly, nilotinib (2nd generation ABL1/2 inhibitor) reverses resistance, in vivo, causing prolonged regression of resistant tumors, and also, prevents BRAFi/MEKi resistance from developing in the first place. These data indicate that repurposing the FDA-approved leukemia drug, nilotinib, may be effective for prolonging survival for patients harboring BRAF-mutant melanomas.
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PMID:Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling. 3312 28


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