Isolation and biochemical characterization of leukemia-associated inhibitory activity that suppresses colony and cluster formation of cells

Bognacki, John; Broxmeyer, Hal E.; LoBue, Joseph

doi:10.1016/0304-4165(81)90391-3

Cited by 20 publications

(14 citation statements)

References 16 publications

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“…Acidic isoferritins are inactive against CFU-GM from nonremission patients with acute leukemia and from some patients with chronic leukemia and acute leukemia in remission (11)(12)(13)26). Inactivity was not related to cycle status of patient CFU-GM as CFU-GM upon removal from patients were in cycle (11).…”

Section: Resultsmentioning

confidence: 92%

“…An example of this is a leukemia-associated inhibitory activity (10)(11)(12), which has recently been identified as acidic isoferritins (13). Acidic-isoferritin inhibitory activity can be found in normal bone marrow and blood cells but is present in much greater concentrations in such cells from patients with acute and chronic myeloid and lymphoid leukemia (10,11,13).…”

mentioning

confidence: 99%

“…This activity has also been detected in mice infected with Abelson and Friend virus (14,15). In contrast to its inhibitory action on normal CFU-GM, which is restricted to the DNA synthetic phase of the cell cycle (S-phase), acidic isoferritin inhibitory activity is not effective in suppressing the growth of CFU-GM from many patients with leukemia and from mice infected with Abelson and Friend virus and blast progenitor cells even though the CFU-GM and blast progenitor cells are in cycle (10)(11)(12)(13)(14)(15)(16). The mechanisms involved in the lack of responsiveness of "leukemia" CFU-GM to inhibition by acidic isoferritins have not been elucidated but would be of importance for a better understanding of the progression of leukemia.…”

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confidence: 99%

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Relationship of Cell-Cycle Expression of Ia-like Antigenic Determinants on Normal and Leukemia Human Granulocyte-Macrophage Progenitor Cells to Regulation In Vitro by Acidic Isoferritins

Broxmeyer

1982

J. Clin. Invest.

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A B S T R A C T An association has been established between human Ia-like (Ia) antigenic determinants, expression during DNA synthesis on granulocyte-macrophage colony forming cells (CFU-GM) and the regulatory action of acidic isoferritins in vitro. Treatment of human bone marrow cells with monoclonal-anti-lalike (Ia) plus complement inhibited colony and cluster formation by -50% but did not affect pre-CFU-GM. Reduction of colonies and clusters was similar whether bone marrow cells were exposed to anti-Ia plus complement, high specific activity tritiated thymidine (3HTdr) or acidic isoferritins. No further decrease was apparent with 3HTdr or acidic isoferritins after Ia-antigen+ CFU-GM were removed, or with anti-Ia plus complement or acidic isoferritins after DNA synthetic phase (S-phase) CFU-GM were removed. Anti-Ia, without complement, did not reduce colony or cluster formation but did block the inhibitory action of acidic isoferritins. A relationship existed between Ia antigens and the activity of acidic isoferritins in the following ways: (a) The apparent loss of Ia-antigens from CFU-GM by 5 h in culture at 37°C, but not at 270 or 4°C, was associated with nonresponsiveness to inhibition with acidic isoferritins, (b) Ia-antigen-, noncycling pre-CFU-GM that were insensitive to acidic isoferritins could generate a population of Ia-antigen+ cycling CFU-GM in vitro that were responsive to inhibition by acidic isoferritins, and (c) nondetectability of Iaantigens on CFU-GM from patients with leukemia was associated with nonresponsiveness to inhibition by acidic isoferritins. These results implicate Ia-antigen' progenitor cells in the regulation of myelopoiesis in vitro and demonstrate that absence of Ia-antigens on patient CFU-GM is associated with im-

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Section: Resultsmentioning

confidence: 92%

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confidence: 99%

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confidence: 99%

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Relationship of Cell-Cycle Expression of Ia-like Antigenic Determinants on Normal and Leukemia Human Granulocyte-Macrophage Progenitor Cells to Regulation In Vitro by Acidic Isoferritins

Broxmeyer

1982

J. Clin. Invest.

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“…However, investigation of these effects directly in the agar cultures is severely impaired by the semisolid agar matrix. The addition of prostaglandin E and acidic isoferritins to agar cultures at time points [12][13][14][15][16][17][18][19][20][21][22][23][24] h after initiation has no effect on CFU-GM proliferation (unpublished observation). This result may occur as a result of loss of CFU-GM Ia-antigen expression (8,11).…”

Section: Discussionmentioning

confidence: 99%

“…Prostaglandins, dibutyryl-3'-5'-cyclic adenosine monophosphate and indomethacin were purchased from Sigma Chemical Co., St. Louis, MO. A standard source of acidic isoferritins (pH < 5.0 after isoelectric focusing) was used throughout these studies (13,19). This fraction of ferritin was kindly provided by Dr …”

Section: Methodsmentioning

confidence: 99%

Association between colony forming units-granulocyte macrophage expression of Ia-like (HLA-DR) antigen and control of granulocyte and macrophage production. A new role for prostaglandin E.

Pelus¹

1982

J. Clin. Invest.

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A B S T R A C T The expression of Ia-like antigens on human colony forming units-granulocyte macrophage (CFU-GM) is related to S-phase of the cell cycle, and associated with the control of normal granulocyte and macrophage production by prostaglandin E and acidic isoferritins in vitro. Ia-antigen expression by CFU-GM is lost within 3-6 h of culture at 370C and occurs simultaneously with loss of responsiveness to inhibition by these factors. Culture of bone marrow CFU-GM in a limited exposure suspension culture with 1 AM-lpM prostaglandin E (PGE1 or PGE2), but not prostaglandin F2a or dibutyryl-cyclic-3'-5'-AMP results in the detection of CFU-GM Ia-antigen after 24 h. Antigen expression is associated with an absolute increase in total and S-phase CFU-GM, and restoration of responsiveness to inhibition by prostaglandin E and acidic isoferritins. The detection of Ia-antigen on CFU-GM after suspension culture with prostaglandin E results both from Iaantigen reexpression as well as stimulation of noncycling cells to enter S-phase, express Ia-antigen and give rise to CFU-GM sensitive to inhibition by prostaglandin E and acidic isoferritins. The sensitivity of CFU-GM to inhibition by these factors after suspension culture with prostaglandin E is identical to that of the same cells tested prior to the suspension culture. These studies provide evidence for a direct regulatory association between Ia-antigen expression and control of myeloid progenitor cell differentiation, and suggest a role for prostaglandin E in the control of CFU-GM cell cycle, Ia-antigen expression, and growth regulation.

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Acute myeloid leukemia as the first hematologic manifestation of fanconi anemia

et al. 1982

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A six-year-old girl with Fanconi anemia (FA) developed acute myeloid leukemia (AML) as the first hematologic manifestation of the syndrome. She remains in remission 18 mo after diagnosis although her management is complicated by unusual sensitivity to chemotherapeutic agents. Marrow cells studied prior to initiation of leukemia therapy showed increased chromosome breakage and an abnormal clone in which a number 7 and a number 8 chromosome were replaced by two marker chromosomes. During the present remission her cultured lymphocytes, bone marrow cells, and fibroblasts showed increased "spontaneous" chromosome breakage as well as enhanced sensitivity to the clastogenic effect of the difunctional alkylating agent diepoxybutane (DEB), features characteristic of FA. Eight months into remission 50% of her marrow cells comprised an abnormal clone, which was monosomic for the number 7 chromosome but had both copies of number 8; in addition a variable number of unique marker chromosomes were present in clonal as well as nonclonal cells. This same marrow sample, upon culture, showed an abnormal growth pattern of CFU-GM, absence of detectable CFU-GEMM and BFUe, non-responsiveness of CFU-GM to inhibition by acidic isoferritins, increased bone marrow acidic isoferritin inhibitory activity, and absence of detectable bone marrow cell-derived GM-CSF. The implications of these findings to leukemogenesis in FA are discussed.

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Isolation and biochemical characterization of leukemia-associated inhibitory activity that suppresses colony and cluster formation of cells

Cited by 20 publications

References 16 publications

Relationship of Cell-Cycle Expression of Ia-like Antigenic Determinants on Normal and Leukemia Human Granulocyte-Macrophage Progenitor Cells to Regulation In Vitro by Acidic Isoferritins

Relationship of Cell-Cycle Expression of Ia-like Antigenic Determinants on Normal and Leukemia Human Granulocyte-Macrophage Progenitor Cells to Regulation In Vitro by Acidic Isoferritins

Association between colony forming units-granulocyte macrophage expression of Ia-like (HLA-DR) antigen and control of granulocyte and macrophage production. A new role for prostaglandin E.

Acute myeloid leukemia as the first hematologic manifestation of fanconi anemia

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