Allogeneic Transplanst for ACUTE Myeloid Leukemia: Cut Off Levels of WT1 Expression in 207 Patients and Pre-Emptive Therapy of Relapse

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1866-1866
Author(s):  
Carmen Di Grazia ◽  
Simona Geroldi ◽  
Raffaella Grasso ◽  
Maurizio Miglino ◽  
Nicoletta Colombo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Cell Transplant ◽  
Allogeneic Hsct ◽  
Group A ◽  
Leukemia Relapse ◽  
Group B ◽  
Acute Myeloid ◽  
Marrow Cells

Abstract Leukemia relapse remains a significant problem in patients with AML undergoing an allogeneic stem cell transplant(HSCT). Wilms Tumour 1 (WT1) expression has been shown to be a sensitive marker of minimal residual disease (MRD), both in patients after induction chemotherapy, as well as in patients undergoing an allogeneic HSCT. Hypotheses. The present study had 2 hypotheses: (1) WT1 expression in marrow cells of AML patients post-HSCT, will predict leukemia relapse and (2) WT1 based pre-emptive immunotherapy (IT) such as abrupt cyclosporin discontinuation and/or donor lymphocyte infusion (DLI), will prevent leukemia relapse. Patients. Bone marrow WT1 expression, was monitored in 207 patients with acute myeloid leukemia (AML) before and monthly after an allogeneic HSCT, until day +150, and then at every other outpatient access. Eligible for IT were patients without acute or chronic GvHD, with increased WT1 expression and a a marrow in hematologic remission. The trigger for IT was 180 WT1 copies in a first group of 122 patients (group A): this was based on the fact that WT1 expression in normal bone marrow is up to 180 copies . In a subsequent group of 85 patients (group B) the cut off for IT, was 100 copies, due to the fact that a first analysis of group A had shown 100 copies to be an earlier predictor of relapse (BJH 2013; 160: 503). DLI were given in escalating doses, starting at 1x105 CD3+ cells/kg in alternative donor grafts and at 1x106/kg in HLA identical grafts. DLI were escalated ½ log every month, in the absence of GvHD, to a maximum dose of 1x107/kg. Sixtyfour patients were eligible for IT, but only 35 received IT: reasons for non intervention were ongoing GHD, unavailable donor and delay in WT1 results. Results-Hypothesis N.1. Following transplantation, WT1 expression, was highly predictive of leukemia relapse: 12 relapses in 99 patients with WT1 < 100 copies /104 abl (12%); 19 relapses in 55 patients with WT1 between 101 and 180 copies (35%) and 37 relapses in 53 patients with WT1 >180 copies (70%) (p<0.0001). The median interval between WT1 positivity and relapse was 75 days in group A and 60 days in group B. Results-Hypothesis N.2. 35 patients received pre-emptive immune intervention, 17 in group A and 18 in group B. The latter had more patients beyond first remission at transplant (56% vs 23%) , more myeloablative regimens (100% vs 65%) and more family haploidentical donors (72% vs 6%); age was comparable. The risk of relapse was 13/17 (76%) for group A and 3/18 (17%) for group B (p<0.001), despite the larger proportion of patients beyond CR1 at transplant. GvHD following DLI occurred in 15% of patients. DLI-related mortality was 0%. The overall 3 year survival for patients in group A and B was 69% vs 47% (p=0.3). The relapse risk in patients of group A eligible but not receiving IT (n=21) was 74%; in group B (n=8) it was 50%. In conclusion, WT1 expression post-transplant is a strong predictor of leukemia relapse in patients with AML, and can be used to trigger pre-emptive immunotherapy, in approximately 50% of eligible patients. IT triggered at a WT1 cut-off level of 100 copies in bone marrow cells, is more effective, as compared to180 copies, in preventing leukemia relapse. Disclosures No relevant conflicts of interest to declare.

No Significant Difference in Therapy Results between Acute Myeloid Leukemia Patients with Myeloblastic Bone Marrow Infiltration within the Range of 20–29% and over 29% at Diagnosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4564-4564
Author(s):  
Sebastian Grosicki ◽  
Jerzy Holowiecki ◽  
Slawomira Kyrcz-Krzemien
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Clinical Symptoms ◽  
Bone Marrow Infiltration ◽  
Acute Leukemias ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Acute Myeloid

Abstract Definition of acute myeloid leukemia (AML) includes a heterogenous group of disorders differing in cytogenetics, clinical symptoms and prognosis. A common feature is bone marrow infiltration with leukemic clone which is also present in peripheral blood and different organs. Over thirty years ago the FAB (French-American-British) group defined the morpho-cytochemical classification of acute leukemias and proposed ≥30% leukemic blasts in bone marrow for a threshold between muelodysplastic syndromes and acute leukemias. In 2002 the WHO group of experts decided to decrease this border line to 20%. The question concerning differences in results of particular treatment programs for AML patient subgroups with original blastic bone marrow infiltration within the range of 20–29% and ≥30% remains disputable. To address this question we performed an analysis in 405 patients treated according to the PALG (Polish Adult Leukemia Group) protocol DAC and DA. At diagnosis there were 26 patients with myeloblastic bone marrow infiltration ranging 20–29% (group A) and 379 patients with infiltration ≥30% (group B). In 62,5% patients (n=10) of the group A AML was preceding by myelodysplastic syndrome. In the time period 1999–2002 patients under study received as induction DAC-7 regimen: daunorubicin 60 mg/m2/d iv 1–3; cytarabine 200 mg/m2/d ci 1–7; cladribine 5 mg/m2 2h inf. iv d 1–5 or standard DA-7 regimen (the same regimen without cladribine). Patients achieving CR received two courses of subsequent intensive consolidation:HAM (HD AraC, mitoxantrone)HD AraC with or without cladribine in the DAC-7 or DA-7 arm, respectively.In the case of PR after the first induction course the same regimen was repeated. Post-consolidation therapy was in both arms comparable. Complete remission (CR) rate was comparable in both populations and reached 73% in the group A and 70% in group B. There were also no statistical differences between overall survival (OS) and leukemia free survival (LFS) between both groups. OS after 5 years equals 34% in group A and 27% in droup B and LFS 42% and 27%, respectively (p=NS). Our study proves that there are no differences in treatment results between AML patients with original bone marrow infiltration within 20–29% and ≥30% given the same treatment. It confirms that the revised WHO criteria are reasonable.

scholarly journals Improved Outcome in Young Children Compared to Adolescents and Adults After Allogeneic Hematopoietic Stem Cell Transplant for Acute Myeloid Leukemia: a Retrospective Study From Francophone Society of Bone Marrow Transplantation and Cell Therapy (SFGM-TC) (SFGM-TC)

2021 ◽  
Author(s):  
Cécile POCHON ◽  
Marie Detrait ◽  
Jean-Hugues Dalle ◽  
Gérard Michel ◽  
Nathalie Dhédin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Retrospective Study ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Cell Transplant ◽  
Intermediate Risk ◽  
Allogeneic Hsct ◽  
Acute Myeloid

Abstract Background: There are currently few data on the outcome of acute myeloid leukemia (AML) in adolescents and young adults (AYAs) after allogeneic HSCT. The aim of this study is to describe the outcome and its specific risk factors for children, AYAs and adults after a first allogeneic HSCT for AML. Methods: In this retrospective study, we compared the outcome of AML patients receiving a first allogeneic HSCT between 2005 and 2017 according to their age at transplantation’s time: children (<15 years, n=564), AYAs (15-25 years, n=647) and adults (26-40 years; n= 1434). Results: With a median follow-up of 4.37 years (min-max 0.18 – 14.73 years), the probability of 2 year-overall survival (OS) was 71.4% in children, 61.1% in AYAs and 62.9% in adults (p=0.0009 for intergroup difference). Both relapse and non-relapse mortality (NRM) Cumulative Incidence (CI) estimated at 2 years were different between the age groups (30.8% for children, 35.2% for AYAs and 29.4% for adults - p=0.0254, and 7.0% for children, 10.6% for AYAs and 14.2% for adults, p<0.0001; respectively). Whilst there was no difference between the 3 groups for grade I to IV acute GVHD CI at 3 months, the chronic GVHD CI at 2 years was higher in AYAs and adults (31.4% and 36.4%, respectively) in comparison to the children (17.5%) (p<0.0001). In multivariable analysis, factors associated with death were AML cytogenetics (HR1.73 [1.29-2.32] for intermediate risk 1, HR 1.50 [1.13-2.01] for intermediate risk 2, HR 2.22 [1.70-2.89] for high cytogenetics risk compared to low risk), use of TBI ≥ 8 Grays (HR 1.33 [1.09-1.61]), disease status at transplant (HR 1.40 [1.10-1.78] for second Complete Remission (CR), HR 2.26 [1.02-4.98] for third CR and HR 3.07 [2.44-3.85] for active disease, compared to first CR), graft source (HR 1.26 [1.05-1.50] for Peripheral Blood Stem Cells compared to Bone Marrow) and donor age (HR 1.01 (1-1.02] by increase of one year). Conclusion: Age is an independent risk factor for NRM and extensive chronic GVHD. This study suggests that AYAs AML patients should be treated with chemotherapy-based MAC regimen and bone marrow as stem cells source.

scholarly journals Safety and Cost Effectiveness of a 10 × 109/L Trigger for Prophylactic Platelet Transfusions Compared With the Traditional 20 × 109/L Trigger: A Prospective Comparative Trial in 105 Patients With Acute Myeloid Leukemia

Blood ◽  
1998 ◽  
Vol 91 (10) ◽  
pp. 3601-3606 ◽  
Author(s):  
Hannes Wandt ◽  
Markus Frank ◽  
Gerhard Ehninger ◽  
Christiane Schneider ◽  
Norbert Brack ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Blood Cell ◽  
Red Blood Cell ◽  
Myeloid Leukemia ◽  
Platelet Transfusion ◽  
Bleeding Complications ◽  
Group A ◽  
Red Blood Cell Transfusions ◽  
Group B ◽  
Acute Myeloid

Abstract In 105 consecutive patients with de novo acute myeloid leukemia (French-American-British M3 excluded), we compared prospectively the risk of bleeding complications, the number of platelet and red blood cell transfusions administered, and the costs of transfusions using two different prophylactic platelet transfusion protocols. Two hundred sixteen cycles of induction or consolidation chemotherapy and 3,843 days of thrombocytopenia less than 25 × 109/L were evaluated. At the start of the study, each of the 17 participating centers decided whether they would use a 10 × 109/L prophylactic platelet transfusion trigger (group A/8 centers) or a 20 × 109/L trigger (group B/9 centers). Bleeding complications (World Health Organization grade 2-4) during treatment cycles were comparable in the two groups: 20 of 110 (18%) in group A and 18 of 106 (17%) in group B (P = .8). Serious bleeding events (grade 3-4) were generally not related to the patient's platelet count but were the consequence of local lesions and plasma coagulation factor deficiencies due to sepsis. Eighty-six percent of the serious bleeding episodes occurred during induction chemotherapy. No patient died of a bleeding complication. There were no significant differences in the number of red blood cell transfusions administered between the two groups, but there were significant differences in the number of platelet transfusions administered per treatment cycle: pooled random donor platelet concentrates averaged 15.4 versus 25.4 (P < .01) and apheresis platelets averaged 3.0 versus 4.8 (P < .05) for group A versus group B, respectively. This resulted in the cost of platelet therapy being one third lower in group A compared with group B without any associated increase in bleeding risk.

The Growth Inhibition and Apoptosis Induction of Acute Myeloid Leukemia Blast Population by the Blocking IGF-IR Pathway.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4515-4515
Author(s):  
Si Sun ◽  
Yanli He ◽  
Xingbing Wang ◽  
Wei Liu ◽  
Jun Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Pi3k Pathway ◽  
Leukemia Cell Line ◽  
Free System ◽  
Acute Myeloid ◽  
Marrow Cells

Abstract The insulin-like growth factor-1receptor (IGF-1R) is overexpressed in a variety of tumors and has been associated with cancer development. Here, we analysis the IGF-IR expression on the bone marrow cells from 45 newly diagnosed patients with acute myeloid leukemia (AML) by flow cytometry. IGF-1R universally expressed on AML blasts and the leukemia cell line HL-60, did not show significant correlation with FAB subtypes. However, the bone marrow cells from AML patients with high myeloblast counts (&gt;80%) generally showed brighter IGF-IR expressions, which indicated the IGF-IR pathway might play an important role for AML blast proliferation and survival. Indeed, blocking the IGF-1R pathway by neutralizing monoclonal antibodies could reduce the proliferation of HL-60 cells by 38.28% at 48 hr. This inhibitory effect on blast growth was observed in 4 of 5 AML samples. In the same IGF-1R blocking treatment, the apoptosis of HL-60 cells was significantly induced, resulting in apoptosis of 57% of the cell population with the measurement of Annexin V vs PI staining by flow cytometry. The control contained only 20% apoptotic cells. We also demonstrated that the blockade of the IGF-1R pathway inhibited the phophorylation of the PI3K pathway component Akt in HL-60 cells when cultured in a serum free system with a supplement of 50ng/ml exogenous IGF. Since PI3K pathway activation greatly contributes to the proliferation, survival and drug resistance of AML, it is of interest to study whether blockading IGF-IR could also inhibit the PI3K pathway in primary AML blasts and synergize other anti-leukemia agents to improve the therapeutic effectiveness. Conclusions: IGF-IR may play an important role in the proliferation and survival of the AML blast population; Blocking the IGF-IR pathway could significantly inhibit the growth of AML blasts and considerably induce the apoptosis of AML blasts; IGF-IR could become a critical molecular target in anti-leukemia drug discovery.

Treatment of Acute Myeloid Leukemia in a Community Hospital.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4575-4575
Author(s):  
Mandeep S. Dhami ◽  
Anca Bulgaru ◽  
Kandhasamy Jagathambal ◽  
Dinesh Kapur ◽  
Dennis E. Slater ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
Community Hospital ◽  
Care Center ◽  
Tertiary Care ◽  
Cell Transplant ◽  
Number Of Patients ◽  
Acute Myeloid

Abstract Optimal management of patients with acute myeloid leukemia requires an accurate diagnosis along with cytogenetics and an intensive systemic chemotherapy regimen administered by a multidisciplinary team of experienced physicians, nurses and other support staff. It has been suggested that such complex patients should be treated only at tertiary care centers. However, it is often difficult for patients and families to receive care at teratiary care center which may be at a great distance from their home. Here we present a retrospective review of all patients diagnosed and treated for acute myeloid leukemia at William W Backus Hospital, a 213 bed acute care hospital serving a community of 70,000 in Norwich, Connecticut between the years 2000 and 2005. A total of 44 patients were treated during this period. There were 22 males and 22 females. The median age was 67.5 years. Bone Marrow samples were evaluated by a hematopathologist (histopathology, flowcytometry and cytogenetics) at a near-by tertiary care center. FAB subgroups and cytogenetics were similar to other published studies. APML patients are not included in this analysis. The median survival for the entire group was 14.7 months ranging from 2 days to 113 months. Fourteen patients were alive, all in continued clinical remission except one with relapsed disease and one patient remains transfusion dependent. Median survival was 15.2 months for men compared to 13.2 months for women. Four patients were referred for bone marrow/stem cell transplant after induction therapy. The limitation of this study is the relatively small number of patients as one would expect from a study done at a small community hospital. Nevertheless, it appears that the median survival of our patients is similar to a pooled analysis of five SWOG trials published by Gundacker et al. We conclude that most patients with acute myeloid leukemia can be managed in a community hospital with commitment and experience to treat such patients. Treatment outcomes (median survival) Study Number of Patients Under 55 55 – 65 65 – 75 Over 75 *Gundacker et al. Blood, 1 May 2006, volume 107, 3481–3485 Current study 44 17.1 m 18 m 11.7 m 5.7 m Gundacker et al* 968 18.8 m 9.0 m 6.9 m 3.5 m

Acute Myeloid Leukemia with Myelodysplasia-Related Changes (MRC) Did Not Show Inferior Outcomes Compared to Those without MRC,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3563-3563
Author(s):  
Jee Hyun Kong ◽  
Hyun Ae Jung ◽  
Hee Kyung Ahn ◽  
Silvia Park ◽  
Hee-Jin Kim ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Risk Group ◽  
Univariate Analysis ◽  
Group A ◽  
Group B ◽  
Group D ◽  
Acute Myeloid

Abstract Abstract 3563 The distinctive features of the World Health organization (WHO) classification compared to French-America-British Co-operative group (FAB) classification of acute myeloid leukemia is the new morphological entity “AML with multilineage dysplasia (MLD)”, and now this subgroup has been renamed as 'AML with myelodysplasia-related change (MRC)”. It generally accepted that dysplasia was most frequently noted in older individual, is often associated with an unfavorable cytogenetic profiles and unfavourable response to therapy. However it is still controversial. Therefore, we evaluated the impact of MRC on overall survival (OS) and leukemia free survival (LFS) in acute myeloid leukemia patients. A total of 644 adult AML patients diagnosed at Samsung Medical Center (SMC) between Sep.1994 and Oct. 2010 were enrolled. We reviewed their medical histories, clinical parameters, hemogram data, bone marrow aspirate and cytogenetic studies, and reclassified them into AML with of MRC and without MRC groups. Of 664 patients, 543 patients were received induction chemotherapy, among them, 84 patients demonstrated MRC and 451 patients did not. Median age was 50 (15–88) years old, and 57.1% of patients were male. Median follow up period was 77.3 [0–191] months. AML without MRC group had more favorable cytogenetic risk, higher WBC counts and LDH levels than those with MRC. However, other variable such as age, sex, hemoglobin level, absolute neutrophil, and peripheral blast count, induction chemotherapy regimen, hematopoietic stem cell transplantation, CR1 (complete response after induction chemotherapy), CRp (complete recovery of platelet), and relapse rate were not different between two groups. Since FLT3-ITD and NPM1 tests were introduced into laboratory work after 2005, results of these tests were available only in 158 and 75 patients respectively, and these were not different between two groups. In univariate analysis, advanced age (>65 years) predicted worse LFS (median LFS [95% C.I.]; ° Â65 years vs >65 years; 9.3[7.2–11.4] vs 5.9[4.6–7.2] months, p =0.014). In terms of OS, young age (p=0.000), female (p=0.000), favorable cytogenetic risk (p=0.000), CR1 (p=0.000), CRp (p=0.000), absence of relapse (p=0.000), and HSCT (p=0.000) showed a higher probability of longer OS (Table 1). The presence of MRC, FLT3-ITD, and NPM1 did not affect OS (Table 1).Table 1.Summary of univariate analysis for overall survival.Median OS (months) [95% C.I.] or mean OS ± SD (months)pAge°Â65 years47.9 [17.1 – 78.6]0.000>65 years13.1 [5.9 – 20.4]SexMale23.2 [16.5 – 30.0]0.000¢Female112.2 [ – ]Cytogenetic risk¢Favorable107.0±7.40.000Intermediate28.0 [19.0 – 36.9]Unfavorable10.8 [7.8 – 13.7]Unknown17.5 [6.8 – 28.1]MRCAbsence35.9 [6.6 – 65.2]0.081Presence19.0 [6.9 – 31.0]CR1¢Yes112.2 [–]0.000No3.6 [1.1 – 6.1]CRp¢Yes70.9±4.40.000No54.8 [18.5 – 91.1]RelapseYes21.5 [17.2 – 25.9]0.000No17.5 [–]HSCT¢Auto86.2±5.60.000¢Allo83.8±6.5Not done17.5 [10.8 – 24.1]FLT3-ITDPositive8.2 [0–26.1]0.595Negative29.5 [20.9–38]NPM1¢Positive104.1±11.00.978¢Negative78.9±15.0¢“median survival not reached Next, we analyzed MRC effect in each variable to OS. The presence MRC did not affect OS of each group which divided according to the age (Figure 1. A and B), sex, cytogenetic risk groups (Figure 1. C and D), relapse, CR1, HSCT, and FLT3-ITD, though AML with MRC group had tendancy to have poor survival rate in intermediate cytogenetic risk group (Figure 1. C). However in patients who did not acheived CRp or showed NPM1, the presence of MRC correlated with shorter OS.Figure 1.Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D).Figure 1. Overall survival (OS) according to the presence of MRC in age ° Â65 group (A), age>65 group (B), intermediate cytogenetic risk group (C)), and unfavorable cytogenetic risk group (D). In this study, patients with MRC did not show inferior outcomes than those without MRC. Therefore it is not necessary to decide different treatment strategy according to the presence of MRC Disclosures: No relevant conflicts of interest to declare.

Acute Myeloid Leukemia Cells Generate Leukemic Endothelial Cells with Leukemogenic Potential: Blood Vessels As Sanctuaries for Leukemia Relapse

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 241-241
Author(s):  
Christopher R Cogle ◽  
Gerard J Madlambayan ◽  
Devorah C Goldman ◽  
Azzah Al Masri ◽  
Ronald P. Leon ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Endothelial Cell ◽  
Blood Vessels ◽  
Myeloid Leukemia ◽  
Bone Marrow Cells ◽  
Surface Proteins ◽  
Nsg Mice ◽  
Acute Myeloid ◽  
Marrow Cells

Abstract Abstract 241 Human hematopoietic stem cells (HSCs) possess hemangioblast activity, which is defined as the ability to generate both blood and endothelium. Whether malignant HSC counterparts such as acute myeloid leukemia (AML) also display this bipotentiality remains to be defined. To test the hemangioblast potential of AML cells we first cultured primary human AML bone marrow in conditions established by Yoder and colleagues that support the growth of functional endothelial cell (EC) progenitors. AML cultured in endothelial colony forming cell (ECFC) media generated endothelial progenitor cell colonies that showed uptake of acetylated LDL and expressed several EC surface proteins, including CD105, CD146, UEA-1 and CD144. Importantly, ECFCs derived from AML bone marrow no longer expressed CD45 or myeloid surface proteins such as CD14. When placed in Matrigel, these AML derived ECFC generated capillary-like, tubular structures. Moreover, these ECFCs contained cytogenetic mutations associated with their parental leukemias. Thus, under the appropriate conditions, AML bone marrow cells can generate cells with an endothelial-like phenotype and harboring leukemia specific mutations that will be referred to as ‘L-ECFC.' To functionally define leukemia hemangioblast activity, a xenograft model of AML was employed. Sublethally irradiated NOD/scid/IL2Rγ−/− (NSG) mice were transplanted with primary human AML cells and then sacrificed at 8–36 weeks after transplant. Significant accumulations of human AML cells were found in perivascular regions of the liver. Both tight coupling and bona fide cell fusion between AML and ECs was observed. AML derived EC that were integrated into portal vein endothelium showed induction of CD105 expression Follow-up AML xenotransplant experiments with BrdU labeling revealed almost four-fold fewer (6%) of the AML cells incorporated within blood vessels were BrdU+, as compared to AML cells not integrated in blood vessels (22%) (P=0.01). These results suggest that AML cell incorporation within the endovascular lining induces cell quiescence. Thus, leukemia-integrated ECs may be less susceptible to cell cycle active agents like cytarabine. Results from these experiments also raised the possibility that AML cells adopting an endothelial-like phenotype may serve as a reservoir for leukemic relapse. To test this hypothesis, we injected CD105+CD45- L-ECFC derived from AML patients into NSG mice. These L-ECFC generated colonies of human CD105+CD45- within spleens and bone marrow of recipient mice. We also found a distinct population of human CD45+CD19- cells comprising 5–10% of bone marrow cells. Leukemia-derived cells were confirmed by detection of cytogenetically mutant cells consistent with the parent leukemia (e.g., MLL duplications). In conclusion, this study demonstrates that AML cells can functionally generate leukemic ECs that become quiescent after incorporation in blood vessel networks and can re-emerge with a leukemogenic phenotype. Together, our results raise the strong possibility that AML cells exhibit functional hemangioblast activity and that vascular endothelium may serve as a clinically important sanctuary for occult leukemia. Our data also support endothelial cell targeting strategies as a means to eradicate AML. Disclosures: No relevant conflicts of interest to declare.

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