A Possible Correlation Between Growth-Factor Sensitivity and Response to Mitoxantrone Treatment in a Murine Myeloid Leukaemia (SA7HD) Cell Line

Abubakar, Aminu A.; Riches, Andrew

doi:10.3109/02841869709001290

Cited by 1 publication

(14 citation statements)

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“…We have already reported that recurrent SA7HD leukemic cells were not sensitive to proliferative stimulation by WEHI‐CM in vitro (11). The responses of these cells to L‐929‐CM is shown in Fig.…”

Section: Resultsmentioning

confidence: 84%

“…This leukemia is well characterized in terms of its phenotypic difference from the SA7 low‐cell‐dose variety (10), labeling index (11), morphology, and transplantation properties (12).…”

Section: Methodsmentioning

confidence: 99%

“…The drug was serially diluted in normal saline or RPMI medium just before setting up the experiments. A pharmacokinetically relevant concentration range of mitoxantrone (0.12–120 ng/ml) was used in the in vitro cytotoxity assays 11,14).…”

Section: Methodsmentioning

confidence: 99%

“…The cells and supernatant were harvested after 5–6 days. The potency of the supernatant was tested against normal murine bone marrow cells as was described for WEHI‐CM (11).…”

Section: Methodsmentioning

confidence: 99%

“…Although the later was morphologically indistinguishable from the untreated variety, it nevertheless developed altered sensitivity to proliferative stimulation by WEHI‐conditioned medium (WEHI‐CM). In contrast, bone marrow cells of normal mice treated with similar doses and schedule of mitoxantrone remained responsive to growth factor(s) (11). Despite the recovery of growth‐factor sensitivity as a result of a single passage of the recurrent leukemia in normal mice, these cells have already developed resistance to mitoxantrone.…”

Section: Introductionmentioning

confidence: 99%

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Loss of growth factor sensitivity and development of mitoxantrone resistance in transplanted recurrent SA7HD myeloid leukaemia

Abubakar¹

2002

J Exp Therapeutics

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Recurrent SA7HD leukemia cells have also "lost" the response to stimulation by L-929-conditioned medium (L-929-CM) and indeed were significantly insensitive to proliferative stimulation by combinations of WEHI-conditioned medium (WEHI-CM) and L-929-CM (P = 0.04) in contrast to untreated SA7HD leukemia, which displayed dose-dependent stimulation by L-929-CM and exhibited synergistic proliferative response to combinations of the two growth factors. This altered growth-factor sensitivity, which was a function of both the route of leukemia inoculation and drug administration, was detected by both the colony and the tritiated thymidine (3HTdR) incorporation assays. In contrast to transplant in normal mice, recurrent leukemia transplanted in mitoxantrone pretreated mice remained growth-factor insensitive. In addition, no growth delay of the recurrent leukemia occurred during this passage in pretreated mice. However, recovery of growth-factor sensitivity still occurred after a single subsequent transplant in normal mice. The magnitude of resistance developed by the recurrent leukemia was not increased by passage in mitoxantrone pretreated mice. Rather, the extent of resistance was a function of the dose of mitoxantrone employed in the treatment of the leukemia before recurrence. These data interpreted along with previously published observations suggest that the development of altered growth-factor sensitivity by SA7HD recurrent leukemia was directly linked to the presence of mitoxantrone. In addition, this phenomenon possibly confers survival advantage to the leukemia cells and this probably accounts for the observation that most of the drug-treated mice ultimately developed recurrent disease despite adequate treatment.

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Section: Resultsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…The cells and supernatant were harvested after 5–6 days. The potency of the supernatant was tested against normal murine bone marrow cells as was described for WEHI‐CM (11).…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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