Do we treat a disease or a patient? A subtle difference with dramatic consequences

Degos, L

doi:10.1038/sj.thj.6200024

Cited by 2 publications

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“…65 De-selection of therapies -principally fludarabine and cladribine -in the minority of patients test-resistant to these drugs could improve outcome and may therefore improve survival. 14,15 The molecular basis for resistance against these compounds remains, however, to be established.…”

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confidence: 99%

Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia

et al. 2002

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In B-CLL, non-proliferating B cells accumulate due to defective apoptosis. Cytotoxic therapies trigger apoptosis and deregulation of apoptotic pathways contributes to chemoresistance. Loss of the apoptosis-promoting Bax has been implicated in resistance to cytotoxic therapy. We therefore evaluated ex vivo drug sensitivity of CLL, producing chemoresponse data which are prognostic indicators for B-CLL, in particular in the case of purine nucleoside analogs. To analyze the underlying mechanisms of drug resistance, we compared endogenous Bax and Bcl-2 expression to ex vivo response to eight drugs, and to survival in 39 B-CLL patients. We found that reduced Bax levels correlated well with ex vivo resistance to traditional B-CLL therapies -anthracyclines, alkylating agents and vincristine (all P Ͻ 0.04). Surprisingly, no such relationship was observed for the purine nucleoside analogs or corticosteroids (all P Ͼ 0.5). Mutational analysis of p53 could not explain the loss of Bax protein expression. Levels of Bcl-2 were not associated with sensitivity to any drug. In contrast to the ex vivo data, neither Bax or Bcl-2 expression nor doxorubicin sensitivity were associated with increased survival whereas sensitivity to fludarabine correlated with better overall survival (P = 0.031). These findings suggest that the resistance to purine nucleoside analogs and corticosteroids in B-CLL is due to inactivation of pathways different from those activated by anthracyclines, vinca alkaloids and alkylating agents and may be the molecular rationale for the efficacy of purine analogs in this disease.

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Section: Spotlightmentioning

confidence: 99%

Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia

et al. 2002

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Diagnosis and treatment of macrocytic anemias in adults

Nagao

Hirokawa

2017

J of Gen and Family Med

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Anemia is one of the most common health problems in the primary care setting. Macrocytosis in adults is defined as a red blood cell (RBC) mean corpuscular volume (MCV) >100 femtoliter (fL). Macrocytic anemias are generally classified into megaloblastic or nonmegaloblastic anemia. Megaloblastic anemia is caused by deficiency or impaired utilization of vitamin B12 and/or folate, whereas nonmegaloblastic macrocytic anemia is caused by various diseases such as myelodysplastic syndrome (MDS), liver dysfunction, alcoholism, hypothyroidism, certain drugs, and by less commonly inherited disorders of DNA synthesis. Macrocytic anemias are treated with cause‐specific therapies, and it is crucial to differentiate nonmegaloblastic from megaloblastic anemia. Because MDS and myeloid neoplasms commonly affect the elderly, primary care physicians may encounter more cases of macrocytic anemias in the near future, as the older population increases. When MDS is suspected along with leukocytopenia and/or thrombocytopenia with anemia, a hematology consultation may be appropriate.

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Do we treat a disease or a patient? A subtle difference with dramatic consequences

Cited by 2 publications

References 0 publications

Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia

Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia

Diagnosis and treatment of macrocytic anemias in adults

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