scholarly journals The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1684-1690 ◽  
Author(s):  
HG Ahuja ◽  
A Foti ◽  
M Bar-Eli ◽  
MJ Cline
Keyword(s):  
Direct Sequencing ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Ras Gene ◽  
Ras Genes

DNA from 161 patients with various forms of hematologic malignancies were investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene were identified in 18 of the 161 patients. The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%. No correlation was observed between the presence of mutations and cytologic features or immunophenotype of these malignancies. Mutations involving codons 12 or 13 were equally prevalent, with a glycine to aspartic acid substitution being the most frequently encountered change. A single T-ALL case had a codon 11 mutation resulting in substitution of alanine with threonine. We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene. Also, no mutations were identified in chronic phase of CML, chronic lymphocytic leukemia. Ph1 positive ALL, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma. These results indicate that RAS mutations, especially those involving exon 1 of the N-RAS gene, are frequent only in a subset of hematologic malignancies.

scholarly journals The pattern of mutational involvement of RAS genes in human hematologic malignancies determined by DNA amplification and direct sequencing

Blood ◽  
1990 ◽  
Vol 75 (8) ◽  
pp. 1684-1690 ◽  
Author(s):  
HG Ahuja ◽  
A Foti ◽  
M Bar-Eli ◽  
MJ Cline
Keyword(s):  
Direct Sequencing ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Ras Gene ◽  
Ras Genes

Abstract DNA from 161 patients with various forms of hematologic malignancies were investigated for mutations in exons 1 and 2 of the N-RAS, K-RAS and Ha-RAS gene by direct sequencing of DNA amplified in vitro by the polymerase chain reaction. Mutations involving either codons 11, 12, or 13 of the N-RAS gene were identified in 18 of the 161 patients. The relative frequencies of N-RAS gene mutations in these hematologic disorders was as follows: acute myelogenous leukemia (AML), 15%; acute lymphoblastic leukemia (ALL), 14%; myelodysplastic syndromes, 24%; and myeloid and lymphoid blast crisis of chronic myelogenous leukemia (CML), 3%. No correlation was observed between the presence of mutations and cytologic features or immunophenotype of these malignancies. Mutations involving codons 12 or 13 were equally prevalent, with a glycine to aspartic acid substitution being the most frequently encountered change. A single T-ALL case had a codon 11 mutation resulting in substitution of alanine with threonine. We failed to find mutations in exons 1 and 2 of the K-RAS or Ha-RAS genes in any case except a single AML with a mutation in codon 61 of the K-RAS gene. Also, no mutations were identified in chronic phase of CML, chronic lymphocytic leukemia. Ph1 positive ALL, non-Hodgkin's lymphoma, Hodgkin's disease, or multiple myeloma. These results indicate that RAS mutations, especially those involving exon 1 of the N-RAS gene, are frequent only in a subset of hematologic malignancies.

scholarly journals Production of Colony-stimulating Factor by Malignant Leukocytes

Blood ◽  
1974 ◽  
Vol 43 (5) ◽  
pp. 749-756 ◽  
Author(s):  
David W. Golde ◽  
Belina Rothman ◽  
Martin J. Cline
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Leukemic Cells ◽  
Colony Stimulating Factor ◽  
Stimulating Factor ◽  
Csf Production

Abstract There is considerable evidence supporting a role for colony-stimulating factor (CSF) as a humoral regulator of leukopoiesis. Data on CSF levels in the serum and urine of patients with leukemia and on the in vitro responsiveness of leukemic cells to CSF have suggested a basis for considering leukemia as a primary disorder of leukopoietic regulation. We examined the question of leukemic cell production of CSF. Conditioned medium from cultured leukemic cells was tested for colony-stimulating activity against normal human bone marrow using a two-layer agar colony assay technique. The cells from patients with acute myelogenous leukemia and a patient with chronic myelogenous leukemia in blast crisis did not elaborate CSF nor did acute lymphocytic leukemia cells. CSF production was documented with cells obtained from patients with chronic myelogenous leukemia in the chronic phase and two patients with acute myelomonocytic leukemia. In acute leukemia the cellular production of CSF correlated closely with morphologic and functional maturation along the monocyte-macrophage line. Evidence was obtained that the adherent cells within the leukemic population were primarily responsible for CSF production. We interpret these data to indicate that neoplastic hematopoietic cells may produce CSF in relation to their capacity for mononuclear leukocyte differentiation.

scholarly journals Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1404-1408 ◽  
Author(s):  
K Ha ◽  
MH Freedman ◽  
A Hrincu ◽  
D Petsche ◽  
A Poon ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
B Lineage

Abstract Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in “mixed” blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence- activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.

scholarly journals Separation of lymphoid and myeloid blasts in the mixed blast crisis of chronic myelogenous leukemia: no evidence for Ig gene rearrangement in CALLA-positive blasts

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1404-1408
Author(s):  
K Ha ◽  
MH Freedman ◽  
A Hrincu ◽  
D Petsche ◽  
A Poon ◽  
...  
Keyword(s):  
Chronic Myelogenous Leukemia ◽  
Gene Rearrangement ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Cell Lineage ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Myelogenous ◽  
B Lineage

Recent studies suggest that lymphoid blast crisis cells of chronic myelogenous leukemia (CML) expressing the common acute lymphoblastic leukemia antigen (CALLA) are B precursor cells, based on the demonstration of immunoglobulin (Ig) gene rearrangement similar to common acute lymphocytic leukemia. There is little evidence to suggest whether the cells with similar lymphoid characteristics in the mixed blast crisis of CML are also committed to B cell lineage. A patient in “mixed” blast crisis of CML was studied. On the basis of morphology, cytochemistry, and immunological studies, the blasts were classified as having either lymphoid or myeloid characteristics. A proportion of the leukemic blasts expressed CALLA, whereas others expressed My7 antigen. In order to characterize both populations of cell further, CALLA+ blasts and My7+ (myeloid) blasts were isolated by fluorescence- activated cell sorting. The My7+ cells were highly proliferative in cell culture blast colony assays, retained the Ph1 chromosome, and were indistinguishable from acute myelogenous leukemia blasts. The CALLA+ cells were also Ph1-chromosome positive, but in contrast, were poorly proliferative in vitro. Of particular note was their retention of germline configuration of Ig genes, thus distinguishing them from blasts in the lymphoid crisis of CML. We conclude that the lymphoid component in mixed blast crisis may represent a stage of differentiation prior to commitment to B lineage.

scholarly journals Mutations of the N-ras gene in juvenile chronic myelogenous leukemia

Blood ◽  
1994 ◽  
Vol 83 (8) ◽  
pp. 2248-2254 ◽  
Author(s):  
J Miyauchi ◽  
M Asada ◽  
M Sasaki ◽  
Y Tsunematsu ◽  
S Kojima ◽  
...  
Keyword(s):  
Sequence Analysis ◽  
Chronic Myelogenous Leukemia ◽  
Blast Crisis ◽  
Gene Mutations ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Disease Stage ◽  
Nucleotide Sequence Analysis ◽  
Age Group ◽  
Ras Gene

Juvenile chronic myelogenous leukemia (JCML), a myeloproliferative disorder of childhood, is distinct from adult-type chronic myelogenous leukemia (CML) and bears resemblance to chronic myelomonocytic leukemia (CMMoL). Since mutations in the N-ras gene have been found at high frequencies in CMMoL, but only rarely in CML, we analyzed mutations activating the N-ras gene in 20 patients with JCML. We used the strategy for analysis of gene mutations based on in vitro DNA amplification by polymerase chain reaction (PCR) followed by single- strand conformation polymorphism (SSCP) analysis and/or direct sequence analysis. Nucleotide sequence analysis showed single nucleotide substitutions involving codons 12, 13, or 61 in six of 20 patients (30%). Four of six patients with mutations were in chronic phase and the other two in blast crisis, indicating no apparent correlation with disease stage. Most of the patients with mutations were in the older age group with poor prognosis, although one patient in the younger age group also harbored the mutation. These data suggest that N-ras gene mutations may be involved in the pathogenesis and/or prognosis of JCML and provide further evidence that JCML is an entity distinct from CML.

scholarly journals Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia [published erratum appears in Blood 1989 Aug 15;74(3):1180]

Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1720-1728 ◽  
Author(s):  
KM Sullivan ◽  
PL Weiden ◽  
R Storb ◽  
RP Witherspoon ◽  
A Fefer ◽  
...  
Keyword(s):  
Graft Versus Host Disease ◽  
Marrow Transplantation ◽  
Acute Gvhd ◽  
Blast Crisis ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Host Disease ◽  
Graft Versus Host

Abstract To assess the influence of graft-versus-host disease (GVHD) on recurrent leukemia and survival after allogeneic marrow transplantation, we studied 1,202 patients with acute nonlymphocytic leukemia (ANL), acute lymphocytic leukemia (ALL), and chronic myelogenous leukemia (CML) given unmodified marrow grafts from HLA- identical siblings. Proportional hazards regression models using acute GVHD and chronic GVHD as time-dependent covariates demonstrated a significant association of GVHD with a decreased relative risk (RR, 0.33 to 0.42) of relapse in patients with ANL, ALL, and CML transplanted in advanced disease. Among patients developing either acute or chronic GVHD, treatment failure (that is, mortality or relapse) was decreased in patients with ALL transplanted in relapse (RR = 0.70, P less than .033) and CML in blast crisis (RR = 0.37, P less than .009). This effect was independent of age, sex, preparative regimen, GVHD prophylaxis, or length of follow-up. Five-year actuarial estimates were derived for the subset of 657 patients who survived in remission 150 days after transplant and were at risk for development of chronic GVHD. Among patients with ANL in first remission or CML in chronic phase, GVHD had an adverse effect on survival and no apparent influence on relapse. Among patients with ANL and ALL transplanted in relapse, the probability of relapse after day 150 was 74% without [corrected] GVHD, 45% with acute and chronic GVHD, 35% with [corrected] only acute GVHD, and 34% with only chronic GVHD (P less than .001). Actuarial survival in these four GVHD groups was 25%, 34%, 59%, and 62%, respectively (P less than .009). Among patients with CML in acceleration or blast crisis, the probability of relapse after day 150 was 65% without GVHD and 36% with acute and/or chronic GVHD (P less than .017). We conclude that acute and chronic GVHD were associated with a durable antileukemic effect and improved survival in patients transplanted in advanced stages of ALL and CML.

scholarly journals Diaziquone given as a continuous infusion is an active agent for relapsed adult acute nonlymphocytic leukemia

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 182-187 ◽  
Author(s):  
EJ Lee ◽  
DA Van Echo ◽  
MJ Egorin ◽  
MS Nayar ◽  
P Shulman ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Drug Exposure ◽  
Blast Crisis ◽  
Active Agent ◽  
Maximum Tolerated Dose ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Acute Nonlymphocytic Leukemia ◽  
Nonhematologic Toxicity

Abstract Diaziquone given as a bolus has not been effective in patients with relapsed or refractory leukemia. Because of in vitro data suggesting enhancement of diaziquone-induced cytotoxicity for human and murine leukemia cells with increased duration of drug exposure and the relatively short terminal plasma half-life of diaziquone, 49 patients (34 acute nonlymphocytic leukemia [ANLL], six chronic myelogenous leukemia in blast crisis [CML-B], five acute lymphocytic leukemia [ALL], four 2 degrees ANLL) with leukemia were given diaziquone as a continuous infusion for seven days. The maximum tolerated dose was 28 mg/m2/d for seven days. The dose-limiting toxicity was the duration of bone marrow aplasia (median, 49 days to greater than 500 PMNs in responders; range, 28 to 101 days). Nonhematologic toxicity was minimal. Responses occurred only in patients with relapsed ANLL, of whom 26 were treated at effective doses. There were six complete responses (CR) (23%) and two partial responses (PR) (8%), although five of eight responders never achieved platelet counts greater than 100,000/microL. Thrombocytopenia in these patients was felt to be a manifestation of diaziquone effect, not persistence of leukemia. The median duration of CR was 195 days (range, 88 to 860+). One patient had active CNS leukemia at the start of treatment and has had a durable (28+ month) CR in both sites of disease. Diaziquone produced prolonged aplasia in patients with secondary ANLL and CML-B (five of ten patients died aplastic), whereas patients with ALL all had regrowth of leukemia and two failed to become aplastic. The lack of significant nonhematologic toxicity and the activity in patients with relapsed ANLL render diaziquone of interest as second-line therapy or consolidation therapy in first remission for patients with ANLL.

scholarly journals Expression of axl, a transforming receptor tyrosine kinase, in normal and malignant hematopoiesis

Blood ◽  
1994 ◽  
Vol 84 (6) ◽  
pp. 1931-1941 ◽  
Author(s):  
A Neubauer ◽  
A Fiebeler ◽  
DK Graham ◽  
JP O'Bryan ◽  
CA Schmidt ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Intracellular Signaling ◽  
Myeloid Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Lymphocytic Leukemia ◽  
Myelogenous Leukemia ◽  
Hematopoietic Tissue ◽  
Blood Leukocytes

Abstract We previously reported the cloning, and characterization of a receptor tyrosine kinase, axl, from two patients with chronic myelogenous leukemia. Herein, we describe the expression pattern of axl in normal and malignant hematopoietic tissue axl message is detected in normal human bone marrow but not significantly in normal blood leukocytes. Cell separation experiments showed that axl is expressed in hematopoietic CD34+ progenitor and marrow stromal cells, at low levels in peripheral monocytes, but not in lymphocytes or granulocytes. Consistent with the normal pattern of axl expression, axl RNA was found predominantly in diseases of the myeloid lineage: 39 of 66 (59%) patients with myeloproliferative disorders (acute myeloid leukemia, chronic myeloid leukemia (CML) in chronic phase, CML in myeloid blast crisis, and myelodysplasia) showed significant axl transcription, as compared with 1 of 45 (2%) lymphoid leukemias (chronic lymphocytic leukemia, acute lymphocytic leukemia, and CML in lymphoid blast crisis). Treatment of K562 cells with the phorbol ester, 12-O- tetradecanoylphorbol-13-acetate (TPA), administration of interferon alpha (IFN alpha) to normal monocytes, and treatment of U937 cells with TPA and IFN tau significantly induced axl expression, supporting a role for this kinase in the intracellular signaling of myeloid cells through a variety of biochemical pathways. These results suggest that the axl kinase may be operative in normal and malignant myeloid biology.

Monitoring of Phosphorylated CRKL in Imatinib Resistant Patients with BCR-ABL Positive Leukemias Expressing BCR-ABL Mutants Treated with AMN107.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 497-497
Author(s):  
Paul La Rosée ◽  
Susanne Holm-Eriksen ◽  
Thomas Ernst ◽  
Heiko König ◽  
Philipp Erben ◽  
...  
Keyword(s):  
Phase I ◽  
Direct Sequencing ◽  
Lymphoblastic Leukemia ◽  
Significant Proportion ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Complete Suppression ◽  
Molecular Response ◽  
Imatinib Resistance ◽  
Imatinib Resistant

Abstract AMN107 is a new, highly potent and selective BCR-ABL inhibitor currently in clinical development for the treatment of imatinib-resistant chronic myelogenous leukemia (CML) or Philadelphia positive acute lymphoblastic leukemia ALL (Ph+ALL). Pre-clinical testing has revealed AMN107 to inhibit all but one (T315I) BCR-ABL mutants which have been associated with imatinib resistance. We sought to determine the pharmacodynamic activity of AMN107 by measuring the proportion of phosphorylated CrkL (CrkL-P) as a surrogate of BCR-ABL activity in vivo. Assay validation revealed a CV-value of 13%, which was defined as cut-off value for significant modulation of the Crkl-P/CrkL ratio. A total of 34 patients (median age 61 years, range 35–80) diagnosed with imatinib resistant Ph+ ALL (n=10), CML in chronic phase (n=1), accelerated phase (n=13), myeloid (n=7), or lymphoid blast crisis (n=3) were investigated in a phase I study permitting individual dose escalation (50–1200 mg/day). Proportion of CrkL-P (Crkl-P/total Crkl) was determined by Western blot, ratio BCR-ABL/ABL by quantitative RT-PCR, and mutation status by direct sequencing in 73 peripheral blood or bone marrow samples from baseline and during treatment with AMN107. Median follow up was 89 days (range 13–386). Patients expressed e1a2 (n=7), b2a2 (n=12), b3a2 (n=14), and b2a2&b3a2 (n=1) BCR-ABL transcripts. At baseline, 18 pts exhibited BCR-ABL mutations (P-loop, n=4; T315I, n=3; others, n=11), in 4 pts two different mutations were found in parallel. Prior to treatment with AMN107, the median proportion of CrkL-P indicating BCR-ABL activity was 47% (range 0–69%). Significant reductions of the proportion of CrkL-P were observed from a dose level of 200 mg AMN107/day. CRKL-P (0%) became undetectable during treatment with AMN107 indicating complete suppression of BCR-ABL in 16 pts starting at AMN107 dose levels of 200 (n=1), 400 (n=2), 600 (n=4), 800 (n=8) or 1200 mg/d (n=1). At baseline, patients had unmutated BCR-ABL (n=8), M244V, Y253H, E255K, T315I, M351T, L384M/H396P, A217V/F311L, L324Q/A350V (n=1 each). Undetectability of CrkL-P, correlated with a good molecular response (ratio BCR-ABL/ABL <2%) in 3 pts. We conclude that a minimum of 200 mg of AMN107 is required to induce effective BCR-ABL inhibition in patients. Effectively repressed CrkL phosphorylation in patients lacking molecular response indicates multifactorial resistance mechanisms. Even in patients with BCR-ABL mutations, BCR-ABL may be inactive suggesting alternative signaling pathways that stimulate proliferation. However, treatment with AMN107 is associated with a reduction of the proportion of CrkL-P indicating suppression of BCR-ABL activity in a significant proportion of patients after imatinib resistance. The CrkL phosphorylation status may help to determine alternative treatment strategies including dose optimization in phase I studies.

Use of Ubiquitin-Proteasome System Profiling for Differentiating Between Various Leukemic Processes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4712-4712
Author(s):  
Ke Zhang ◽  
Hagop M. Kantarjian ◽  
Wanlong Ma ◽  
XI Zhang ◽  
Xiuqiang Wang ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Blast Crisis ◽  
Chronic Phase ◽  
Direct Analysis ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Lymphocytic Leukemia ◽  
Ubiquitin Proteasome

Abstract Abstract 4712 The ubiquitin-proteasome system (UPS) plays a major role in cell homeostasis in normal and neoplastic states. Expression and function of the UPS system vary with the specific characteristics of individual cell types, suggesting that determination of UPS “signatures” could be useful in identifying various cell populations. Since direct analysis of cancer cells is often problematic, even in hematologic diseases, we explored the potential of using UPS signatures in plasma to differentiate between various leukemias. We first analyzed plasma UPS profiles of patients with acute myeloid leukemia (AML; n=111), acute lymphoblastic leukemia (ALL; n=29), advanced myelodysplastic syndrome (MDS; n=20), chronic lymphocytic leukemia (CLL; n=118), or chronic myeloid leukemia (CML; n=128; 46 in accelerated/blast crisis [ACC/BL], 82 in chronic phase), and 85 healthy control subjects. Plasma levels of proteasome, ubiquitin (poly-ubiquitin), and the 3 proteasome enzymatic activities (chymotrypsin-like [Ch-L], caspase-like [Cas-L], trypsin-like [Tr-L]) were measured. Specific activities were calculated by normalizing each of the 3 enzyme activities to the levels of proteasome protein in plasma (Ch-L/p, Cas-L/p, and Tr-L/p). These 8 variables were used in multivariate logistic regression models to differentiate between leukemic processes. UPS signatures provided clear differentiation between patients with a leukemic process and normal controls (AUC=0.991), using 6 different variables (Tr-L/P, Ch-L, Ch-L/p, Cas-L, Cas-L/P, ubiquitin). Distinguishing between acute (AML, ALL, MDS) and chronic (CML, CLL) processes was less efficient (AUC=0.853 using Tr-L, Tr-L/P, Cas-L/P, Ch-L/P, proteasome, Ch-L), likely due to the high proportion (36%) of CML patients in ACC/BL phase. However, UPS signatures generally yielded powerful differentiation between individual leukemias (Table). MDS was not well differentiated from AML (AUC=0.791), reflecting the significant biological overlap of these diseases. These data support the potential usefulness of the UPS profile to aid in the differential diagnosis of various leukemias. Disclosures: No relevant conflicts of interest to declare.

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