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B Clarkson

Publications and source records attributed to B Clarkson.

At least 19 recordsLinked to original sources
PubMed2000

Characterization of two novel sublines established from a human megakaryoblastic leukemia cell line transfected with p210(BCR-ABL).

Disease progression in chronic myelogenous leukemia (CML) is usually accompanied by chromosomal abnormalities such as an additional Ph chromosome, trisomies of chromosome 8 or 19, or i(17) in addition to the standard translocation t(9;22) (q34;q11). However, detailed studies of the various steps involved during this evolution are difficult to perform, thereby making the study of cell lines that contain the transposed genes BCR-ABL, especially those of human origin, an important focus. In this analysis we investigated the human megakaryoblastic cell line MO7e and its subline transfected with BCR-ABL, MO7e/p210. Initial studies demonstrated that the phenotype of the MO7e line was consistent with a megakaryocytic lineage as originally described and was growth factor dependent in liquid culture. The MO7e/p210 subline, however, was growth factor independent and could be further separated into two distinct sublines based on expression of glycophorin A using the monoclonal antibody R10. The subline R10 negative (R10-) was similar to the parent line MO7e but R10 positive (R10+) cells had a distinct erythroid phenotype. In addition, the R10- and R10+ sublines demonstrated strikingly different colony morphology when cultured in semisolid medium. Furthermore, R10+ cells had additional chromosomal abnormalities not detected in the R10- population. These results demonstrate that the insertion of the BCR-ABL in this human leukemia cell line resulted in two distinct subpopulations of cells, each now growth factor independent, but one with a phenotype and karyotype identical to the parent cell line and the other with a different phenotype and additional chromosomal abnormalities. These two subpopulations derived from the MO7e/p210 transfected cell line may prove useful in further understanding the multistep events that occur in the progression of this disease.

Chromosome Aberrations↗
PubMed2000

The phosphatidylinositol polyphosphate 5-phosphatase SHIP1 associates with the dok1 phosphoprotein in bcr-Abl transformed cells.

The initial phase of chronic myelogenous leukemia (CML) is triggered by constitutive protein tyrosine kinase activity of the chimeric kinase p210(bcr-abl) (Bcr-Abl). A major substrate of Bcr-Abl was recently identified as the RasGAP-associated 62 kDa docking protein Dok1. Here, we report complex formation between endogenous Dok1 and the SH2 domain-containing phosphatidylinositol polyphosphate 5-phosphatase SHIP1 in hematopoietic cells expressing Bcr-Abl. Expression of Bcr-Abl induced tyrosine phosphorylation of both Dok1 and SHIP1 and the formation of a Dok1/SHIP1 complex. Tyr(P) SHIP1 was also bound to Shc in Bcr-Abl expressing cells. A small amount of Shc/SHIP1/Dok1 trimolecular complex was detected and this was due to binding of Dok1 to SHIP1 that was bound to Shc. In contrast, association of Dok1 with SHIP1 or RasGAP was mutually exclusive. Both the SH2 domain of SHIP1 and the PTB domain of Dok1 were required for complex formation between the two proteins. Neither the specific activity of SHIP1 as an inositol phosphate 5-phosphatase nor the subcellular localization of SHIP1 appeared to be altered by tyrosine phosphorylation. However, the Dok1/SHIP1 complex was only detected in the cytosolic fraction of Bcr-Abl transformed hematopoietic cells. We propose that interaction between Dok1 and SHIP1 modulates the ability of these two proteins to interact with other cytosolic binding partners.

Animals↗
PubMed1999

A novel SH2-containing phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase (SHIP2) is constitutively tyrosine phosphorylated and associated with src homologous and collagen gene (SHC) in chronic myelogenous leukemia progenitor cells.

Because of the probable causal relationship between constitutive p210(bcr/abl) protein tyrosine kinase activity and manifestations of chronic-phase chronic myelogenous leukemia (CML; myeloid expansion), a key goal is to identify relevant p210 substrates in primary chronic-phase CML hematopoietic progenitor cells. We describe here the purification and mass spectrometric identification of a 155-kD tyrosine phosphorylated protein associated with src homologous and collagen gene (SHC) from p210(bcr/abl)-expressing hematopoietic cells as SHIP2, a recently reported, unique SH2-domain-containing protein closely related to phosphatidylinositol polyphosphate 5-phosphatase SHIP. In addition to an N-terminal SH2 domain and a central catalytic region, SHIP2 (like SHIP1) possesses both potential PTB(NPXY) and SH3 domain (PXXP) binding motifs. Thus, two unique 5-ptases with striking structural homology are coexpressed in hematopoietic progenitor cells. Stimulation of human hematopoietic growth factor responsive cell lines with stem cell factor (SCF), interleukin-3 (IL-3), and granulocyte-macrophage colony-stimulating factor (GM-CSF) demonstrate the rapid tyrosine phosphorylation of SHIP2 and its resulting association with SHC. This finding suggests that SHIP2, like that reported for SHIP1 previously, is linked to downstream signaling events after activation of hematopoietic growth factor receptors. However, using antibodies specific to these two proteins, we demonstrate that, whereas SHIP1 and SHIP2 selectively hydrolyze PtdIns(3,4,5)P3 in vitro, only SHIP1 hydrolyzes soluble Ins(1,3,4,5)P4. Such an enzymatic difference raises the possibility that SHIP1 and SHIP2 may serve different functions. Preliminary binding studies using lysates from p210(bcr/abl)-expressing cells indicate that both Ptyr SHIP2 and Ptyr SHIP1 bind to the PTB domain of SHC but not to its SH2 domain. Interestingly, SHIP2 was found to selectively bind to the SH3 domain of ABL, whereas SHIP1 selectively binds to the SH3 domain of Src. Furthermore, in contrast to SHIP1, SHIP2 did not bind to either the N-terminal or C-terminal SH3 domains of GRB2. These observations suggest (1) that SHIP1 and SHIP2 may have a different hierarchy of binding SH3 containing proteins and therefore may modulate different signaling pathways and/or localize to different cellular compartments and (2) that they may be substrates for tyrosine phosphorylation by different tyrosine kinases. Because recent evidence has clearly implicated both PI(3,4, 5)P3 and PI(3,4)P2 in growth factor-mediated signaling, our finding that both SHIP1 and SHIP2 are constitutively tyrosine phosphorylated in CML primary hematopoietic progenitor cells may thus have important implications in p210(bcr/abl)-mediated myeloid expansion.

Collagen↗
PubMed1998

Molecular cloning and characterization of p56dok-2 defines a new family of RasGAP-binding proteins.

Chronic myelogenous leukemia (CML) is a disease characterized by the presence of p210(bcr-abl), a chimeric protein with tyrosine kinase activity. Substrates for p210(bcr-abl) are likely to be involved in the pathogenesis of CML. Here we describe the purification, cDNA cloning, and characterization of a 56-kDa tyrosine phosphorylated protein, p56(dok-2) (Dok-2), from p210(bcr-abl) expressing cells. The human dok-2 cDNA encodes a 412-amino acid protein with a predicted N-terminal pleckstrin homology domain as well as several other features of a signaling molecule, including 13 potential tyrosine phosphorylation sites, six PXXP motifs, and the ability to bind to p120(RasGAP). Dok-2 was shown to be 35% identical to p62(dok-1), a recently identified RasGAP binding protein from CML cells, and analysis of the expressed sequence tag data base revealed the presence of at least four additional proteins containing a Dok homology sequence motif. Dok mRNAs were primarily expressed in tissues of hematopoietic origin. These findings strongly suggest that a family of Dok-related proteins exists that bind to RasGAP and may mediate the effects of p210(bcr-abl) in CML.

Adaptor Proteins, Signal Transducing↗
PubMed1997

p62(dok): a constitutively tyrosine-phosphorylated, GAP-associated protein in chronic myelogenous leukemia progenitor cells.

Characteristic of chronic myelogenous leukemia (CML) is the presence of the chimeric p210(bcr-abl) protein possessing elevated protein tyrosine kinase activity relative to normal c-abl tyrosine kinase. Hematopoietic progenitors isolated from CML patients in the chronic phase contain a constitutively tyrosine-phosphorylated protein that migrates at 62 kDa by SDS-PAGE and associates with the p120 ras GTPase-activating protein (GAP). We have purified p62(dok) from a hematopoietic cell line expressing p210(bcr-abl). p62(dok) is a novel protein with features of a signaling molecule. Association of p62(dok) with GAP correlates with its tyrosine phosphorylation. p62(dok) is rapidly tyrosine-phosphorylated upon activation of the c-Kit receptor, implicating it as a component of a signal transduction pathway downstream of receptor tyrosine kinases.

CSK Tyrosine-Protein Kinase↗
PubMed1996

c-kit ligand stimulates tyrosine phosphorylation of a similar pattern of phosphotyrosyl proteins in primary primitive normal hematopoietic progenitors that are constitutively phosphorylated in comparable primitive progenitors in chronic phase chronic myelogenous leukemia.

Characteristic of Philadelphia (Ph)+ chronic myelogenous leukemia (CML) is the presence of the chimeric BCR/ABL (p210) protein possessing elevated protein tyrosine kinase activity relative to the normal c-abl tyrosine kinase. Our previous studies demonstrated subtle differences in the growth, phenotypic and morphologic characteristics of the most primitive subpopulations of primary lin-Ph+ chronic phase CML blasts and comparable primary lin- normal blasts. Recently, in comparing proteins phosphorylated on tyrosine in these cell populations, we reported a prominent 62 kDa phosphotyrosyl (P-tyr) protein constitutively present in primary primitive lin- CML chronic phase blasts which was virtually undetectable in primary primitive lin- normal blasts. In the present studies, we demonstrate that this P-tyr p62 from primary primitive lin- chronic phase CML blasts co-immunoprecipitates with ras-GAP. Furthermore, in addition to the p210 protein, we show in whole cell lysates the presence of other clearly consistent but less prominent P-tyr proteins with molecular weights of approximately 155, 140, 110, 55 and 45 kDa as well as more minor P-tyr proteins of approximately 190, 85, 52, 42 and 39 kDa constitutively present in primary primitive lin- chronic phase CML blasts. In analyzing proteins tyrosine phosphorylated in primary primitive lin- normal blasts in response to various hematopoietic growth factors, we found a striking similarity in the phosphorylation of four major (approximately 140, 110, 62 and 56 kDa) and three minor (approximately 51, 45 and 42 kDa) P-tyr proteins after stimulation with c-kit ligand and the P-tyr proteins constitutively phosphorylated in primary primitive lin- chronic phase CML blasts. Other growth factors tested (ie GM-CSF, G-CSF, IL-3, FLT3 ligand and EPO) were much less active or stimulated phosphorylation of other proteins. It is provocative that at least seven proteins rapidly and transiently phosphorylated on tyrosine in the c-kit ligand signal transduction pathway in lin- normal blasts may be constitutive substrates for the p210 activated tyrosine kinase in comparable lin- chronic phase CML blasts. In addition, it is intriguing that some of the biological effects on hematopoietic progenitors attributed to the c-kit ligand may be similar to some of the observed biological consequences of the p210 protein, including survival and expansion of a more mature stem cell population, probably at the time of lineage commitment rather than at the level of the earliest self-renewing stem cell.

Cell Lineage↗
PubMed1996

c-kit ligand stimulates tyrosine phosphorylation of the c-Cbl protein in human hematopoietic cells.

c-kit ligand (KL) is a hematopoietic growth factor that plays a major role in the survival, expansion and differentiation of hematopoietic progenitor cells of various lineages. The biological actions elicited by KL are initiated by binding to its cognate receptor, c-kit, which is a transmembrane tyrosine kinase. The resulting ligand/receptor complex rapidly activates the intrinsic kit receptor tyrosine kinase and subsequent phosphorylation of specific intracellular substrates that are involved in downstream signaling events. In the present studies, we demonstrate that KL stimulates the rapid tyrosine phosphorylation of the proto-oncogene, c-Cbl, in two KL-responsive human hematopoietic cell lines, MO7e and TF-1. In both these cell lines we found a constitutive in vivo association between c-Cbl and the adaptor protein Grb2 and demonstrate (in vitro) that c-Cbl binds primarily to the N-terminal SH3 domain of Grb2. Furthermore, the stoichiometry of this association was not significantly affected upon c-kit receptor activation. We also provide evidence that c-Cbl is not stably associated with the kit receptor either prior to or following KL stimulation. Our findings suggest that c-Cbl is an important component in the KL signaling pathway in human hematopoietic progenitor cells.

Adaptor Proteins, Signal Transducing↗
PubMed1994

A 62-kilodalton tyrosine phosphoprotein constitutively present in primary chronic phase chronic myelogenous leukemia enriched lineage negative blast populations.

Ph+ chronic myelogenous leukemia (CML) is associated with the reciprocal translocation between chromosomes 9 and 22 culminating in the production of the chimeric p210bcr/abl protein possessing elevated protein tyrosine kinase activity relative to the normal c-abl tyrosine kinase. Our recent studies have revealed subtle differences in the growth, phenotypic and morphologic characteristics of subpopulations of primary lin- Ph+ chronic phase CML blasts and comparable primary normal blasts. In an attempt to correlate these biologic abnormalities and the presence of the p210bcr/abl protein, we initiated studies to identify differences in proteins constitutively phosphorylated on tyrosine in whole cell lysates of comparable primary early blast subpopulations derived from normal and Ph+ chronic phase CML marrows. Immunoblotting with anti-P-tyr Abs demonstrated a prominent 62 kDa phosphotyrosyl protein (pp62) constitutively present in 11/11 Ph+ chronic phase linblasts while being virtually undetectable in equivalent amounts of protein derived from 15/15 and 2/2 comparable normal and Ph-negative chronic phase blast populations, respectively. Immunoblotting with an Ab reportedly specific for the ras GTPase activating protein (GAP) associated p62 protein revealed that the pp62 present in CML blasts is not immunologically related to the former protein. Although the identity of the pp62 is presently not known, its prominent presence in chronic phase CML blasts, in which the only known molecular abnormality is putatively the p210bcr/abl protein, strongly suggests that it may be a critical p210bcr/abl substrate involved in an early stage of expansion of the Ph+ clone.

Blast Crisis↗
PubMed1993

Characterization of lineage-negative blast subpopulations derived from normal and chronic myelogenous leukemia bone marrows and determination of their responsiveness to human c-kit ligand.

Lineage-negative (lin-) normal and chronic myelogenous leukemia (CML) marrow blast populations were obtained by negative selection and subsequently separated on the basis of size by velocity sedimentation. The three subpopulations of lin- blasts obtained were enriched for F8 (the more primitive small blasts), F11 (blasts intermediate in size), and F13 (the more mature large blasts). We examined the morphological and phenotypic characteristics and cell cycle status of the subpopulations and determined the responsiveness of granulocyte-monocyte progenitors (colony-forming units/granulocyte-macrophage) derived from each subpopulation to mast cell growth factor in combination with granulocyte (G-CSF) or granulocyte-macrophage (GM-CSF) colony-stimulating factors alone and in combination. Morphological assessment revealed that an increased proportion of CML lin- blasts exhibited early cytoplasmic maturation as evidenced by the appearance of azurophilic (nonspecific) granules in the cytoplasm. Although the percentages of CML and normal small blasts expressing CD34 were similar, the proportion of CML lin- blasts expressing CD34 declined in the intermediate and more mature large lin- blast subpopulations by about 50%, whereas the percentage of CD34+ normal blasts remained essentially the same, indicating an earlier loss of CD34 expression by CML lin- blasts. In addition, the percentages of CML small blasts expressing CD33 were higher than normal (26-61% versus 0-16%, respectively), indicating that a higher proportion of CML small lin- blasts had a more mature phenotype. Mast cell growth factor addition to cultures stimulated by G-CSF, GM-CSF, or G-CSF plus GM-CSF, exerted the greatest synergistic effect (increased colony number and size) in the normal small and intermediate lin- blast cultures, but mast cell growth factor had considerably less effect, or no effect, in cultures of comparable CML subpopulations, indicating that CML lin- progenitors had a somewhat lower requirement for multiple growth factors. The findings suggest that the differences observed between normal and CML marrow subpopulations are proportional differences and that a greater proportion of CML lin- blast subpopulations exhibit characteristics associated with a more advanced stage of maturation than comparable normal lin- blast subpopulations.

Bone Marrow↗
PubMed1993

Differences in the composition and in the efficiency of red cell production of normal and CML erythroid progenitor populations are highlighted by response to human c-kit ligand.

Previous studies have suggested that erythroid progenitors derived from patients with chronic myelogenous leukemia (CML) in chronic phase may have reduced proliferative capacity. Considering recent evidence that mast cell growth factor (MGF) enhances the proliferative capacity of normal erythroid burst-forming units (BFU-E), we examined whether MGF could increase the proliferative potential of CML erythroid progenitors to normal capacity. To evaluate the total proliferative capacity achieved, the BFU-E were divided into four subpopulations (XL = extra large, L = large, M = medium, S = small) and colonies were aspirated to determine the cellularity of BFU-E from each subpopulation. MGF alone or in combination with MoT cell line conditioned medium (MoCM) or granulocyte-macrophage colony-stimulating factor (GM-CSF) + interleukin-3 (IL-3) significantly increased the proliferative capacity of erythropoietin (EPO) dependent CML and normal BFU-E. Although the total number of BFU-E generated were similar, the number of BFU-E with high proliferative potential were considerably less in CML BFU-E populations. BFU-E designated XL (129,000-431,000 cells) were only found in MGF cultures and only normal BFU-E had this proliferative capacity. BFU-E designated L were increased in both normal and CML BFU-E populations but less CML BFU-E had this proliferative capacity (mean number 25% of normal) and CML L BFU-E from 2/3 CML patients comprised fewer cells than normal L BFU-E. Normal BFU-E populations comprised 16-24% high proliferative BFU-E (XL + L) in contrast to 4-5% high proliferative BFU-E (L only) comprising CML BFU-E populations.(ABSTRACT TRUNCATED AT 250 WORDS)

Cells, Cultured↗
PubMed1993

Private psychiatric hospitalization of children: predictors of length of stay.

OBJECTIVE: To quantitatively identify predictors and determinants of length of psychiatric hospital stay for children. METHOD: Forty-seven demographic, psychosocial stressor, psychopathology, and disposition variables were statistically reviewed as correlates of length of stay in 100 consecutive discharges from a child psychiatry inpatient service (age range 4-12) in a private hospital. Those with strong statistical significance were then analyzed by multiple regression. RESULTS: Greater severity of psychopathology (measured by the Children's Global Assessment Scale), greater severity of psychosocial stressors (by Axis IV scale), diagnosis of post-traumatic stress disorder, special educational and out-of-home dispositions, and severe tantrums in hospital all strongly predicted longer hospital stay. Diagnosis of adjustment disorder predicted shorter stay. Together these variables explained 57% of the total variance in length of stay. CONCLUSIONS: The most powerful of these predictor variables could potentially be measured at the time of admission, thus permitting accurate prediction of length of stay. A set of models was generated for this purpose.

Child↗
PubMed1993

Cytokinetic considerations relevant to development of a successful therapeutic strategy in chronic myelogenous leukemia (CML).

Despite recent important advances in our understanding of the molecular and biological abnormalities in chronic myelogenous leukemia (CML) this new knowledge has not yet led to significant improvements in treatment. We have reviewed what is known and still unknown about some of the important properties of normal and leukemic stem cells and later progenitor cells that may be relevant to developing improved treatment strategies in the future. Clinical observations and experimental evidence strongly suggest that the major expansion of the CML population takes place in the intermediate and later maturation compartments rather than in the stem cell or early progenitor cell compartments. The expansion occurs slowly, probably taking several years to reach a trillion or more cells, at which time clinical symptoms begin to develop. The maturing leukemic progenitors do not have an increased proliferative rate, but they undergo one or more additional divisions and also live longer than comparable normal progenitors. Although no quantitative assay system is available to study the ultimate proliferative potential of human stem cells, indirect evidence suggests that the behavior of leukemic stem cells is not greatly different from that of normal stem cells. One important difference is that the leukemic stem cells (or early progenitor cells) do not curtail cell production until marrow cell densities are reached that are substantially higher than those at which normal stem cells cease production. Based on these and other considerations a possible future therapeutic strategy is suggested. Any successful treatment program for CML will probably depend on the inclusion of some type of specific drug(s) that will selectively affect leukemic progenitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1993

Integration of molecular and biological abnormalities in quest for selective treatment of chronic myelogenous leukemia (CML).

CML is an excellent target for development of selective treatment because of its highly consistent genetic abnormality t(9;22) and unique fusion gene product, p210bcr/abl, although it is not yet clear what form of specific therapy might be effective. Several components of p210bcr/abl are thought to be essential for its transforming activity: These include the constitutive tyrosine kinase activity of abl and the ability of the first exon for bcr both to specifically bind to abl's SH2 binding domain and possibly also to function as a novel type of serine kinase. Relatively little is yet known about what specific abnormalities in the regulatory pathways are caused by the altered tyrosine kinase activity of p210bcr/abl and other bcr/abl oncoproteins, but whatever its precise mode of action proves to be, p210bcr/abl presumably somehow changes the normal pattern of phosphorylation of key regulatory proteins in the signaling pathways so that the genes which normally direct the orderly sequence of proliferation and maturation of the myeloid progenitors are not properly regulated. The end results of this 'disregulation' are that there is asynchronous or discordant maturation; relative to comparable normal progenitors, a higher proportion of CML progenitors exhibit earlier cytoplasmic and delayed nuclear maturation. The leukemic progenitors do not proliferate more rapidly than comparable normal progenitors or have increased ultimate proliferative potential, but they go through one or more additional divisions during passage through the later maturation compartments and also live longer, resulting in overexpansion of the leukemic population. It is important to recognize the close linkage between maturation and proliferation in designing experiments to correlate the molecular and biological abnormalities and in seeking novel therapies to selectively affect the leukemic progenitors.

Bone Marrow↗
PubMed1993

Linkage of proliferative and maturational abnormalities in chronic myelogenous leukemia and relevance to treatment.

Despite recent advances in our understanding of the molecular and biological abnormalities in chronic myelogenous leukemia (CML) this new knowledge has not yet led to significant improvements in treatment. We have reviewed what is known and still unknown about the molecular and biological abnormalities in CML that may be relevant to developing improved, more selective treatment. CML originates in a multipotential stem cell due to its acquiring a highly consistent specific chromosomal translocation between chromosomes 9 and 22; this results in a fused bcr/abl gene and an abnormal 210 kDa fusion protein which has increased intrinsic protein tyrosine kinase activity compared to the normal c-abl protein. It is still unknown how p210bcr-abl alters the signal transduction pathways, but the main biological abnormality is discordant or asynchronous maturation, with the cytoplasm generally maturing more rapidly than the nucleus. The major expansion of the CML population takes place in the intermediate and later maturation compartments rather than in the stem cell or early progenitor cell compartments. The expansion occurs slowly, probably taking several years to reach a trillion or more cells, at which time clinical symptoms begin to develop. The maturing leukemic progenitors do not have an increased proliferative rate, but they undergo one or more additional divisions and also live longer than comparable normal progenitors. The earliest CML blast cell population we have been able to study has reduced ultimate proliferative capacity compared to a comparable primitive normal blast cell population. Although no quantitative stem cell assay is available, indirect evidence suggests that the CML stem cells' biological behavior may be relatively unaffected or deviate only slightly from normal. The bcr/abl gene and its fusion protein are promising targets for development of novel specific therapies, but before this can be accomplished it will be necessary to understand more completely the molecular and biochemical abnormalities and to correlate them with the biological manifestations of the disease.

Bone Marrow↗
PubMed1992

Constitutive expression of p53 protein in enriched normal human marrow blast cell populations.

Previous studies by others using metabolic labeling, cell lysis, and immunoprecipitation have reported elevated levels of p53 protein in blast cells derived from patients with acute lymphoblastic leukemia (ALL) and acute myeloblastic leukemia (AML), whereas p53 protein was not detected in normal light-density bone marrow cells. In this report, using the same detection methods, we confirm the negligible expression of p53 protein in normal light density marrow cells. However, we find clearly significant levels of p53 protein expression in enriched normal human marrow blast populations. Furthermore, using a panel of p53 specific monoclonal antibodies, we find the p53 protein constitutively synthesized by normal marrow blasts has the immunologic phenotype identified by PAb240 that reportedly recognizes a common conformational-dependent epitope on mutant p53. We have also found that the p53 immunologic subclass identified by PAb240 exists in normal human circulating lymphocytes either resting, serum starved, or PHA activated. In summary, it is clear that (1) normal marrow blast populations provide the appropriate control for assessing the levels of p53 protein expression in leukemic blast cells; and (2) PAb240 cannot be used to distinguish p53 mutated at the DNA level from normal p53 in fresh human hematopoietic cells.

Antibodies, Monoclonal↗
PubMed1992

Reasons that patients with acute myelogenous leukemia do not undergo allogeneic bone marrow transplantation.

BACKGROUND: Numerous reports suggest that allogeneic bone marrow transplantation prolongs the survival of adult patients with acute myelogenous leukemia (AML) in first remission. However, it is unclear how many such patients actually undergo this procedure. METHODS: We reviewed the case records of 350 consecutive adult patients with AML treated with chemotherapy at a single institution from 1979 (when the policy of offering allogeneic transplantation to all such patients in first remission was introduced) through 1990. The criteria for exclusion before transplantation included age greater than 40 and, beginning in 1984, a diagnosis of acute promyelocytic leukemia. RESULTS: One hundred forty-two patients (41 percent of the study population) were 40 years of age or under. HLA testing was performed for 120 of these patients (85 percent). Sixty-seven patients (47 percent) had an HLA-identical sibling as a potential donor. One hundred three patients (73 percent) entered remission during treatment according to one of five chemotherapy protocols. Of the 52 patients who both entered remission and had an HLA match, 30 underwent transplantation while they were in first remission. These 30 patients constituted 21 percent of all study patients 40 years old or under, 29 percent of all patients 40 or under who entered remission, 45 percent of all patients with an HLA match, 58 percent of all patients who had both a remission and a match, and 9 percent of all patients treated according to a protocol. Among patients with a match who did not undergo transplantation, those with primary refractory disease were the largest subgroup. CONCLUSIONS: These findings suggest that allogeneic bone marrow transplantation is performed in less than 60 percent of adult patients with AML who are potentially eligible for the procedure.

Adult↗