Molecular and prognostic correlates of cytogenetic abnormalities in chronic myelomonocytic leukemia: a Mayo Clinic-French Consortium Study

Abstract Background: The prognostic significance of cytogenetic abnormalities in chronic myelomonocytic leukemia (CMML) was recently revisited (AJH, 89; 813-818, 2014 and Blood April, 2013). Using a large Mayo Clinic-French Consortium database, we analyzed the molecular and prognostic correlates of cytogenetic abnormalities in CMML. Methods: CMML diagnosis was according to World Health Organization criteria. Cytogenetic analysis and reporting was done according to the International System for Human Cytogenetic Nomenclature. Statistical analyses considered clinical and laboratory parameters obtained at time of cytogenetic studies. Results: Spectrum and frequency of cytogenetic abnormalities: A total of 409 patients participated in this study including, 268 (66%) from the Mayo Clinic and 141 (34%) from the French CMML consortium. Of these, 396 (97%) had ≥20 metaphases and 13 (3%) had ten to 19, analyzed. One hundred and fifteen (30%) patients displayed an abnormal karyotype, including 82 (71%) sole, 20 (17%) two and 13 (11%) complex abnormalities. The most common abnormalities were; +8 (23%), -Y (20%), -7/7q- (14%), 20q- (8%), +21 (8%) and der (3q) (8%). Other cytogenetic abnormalities included 5q-, 12p-, 13q- and i(17q), present at a much lower frequency (0.9-4%). Phenotypic correlates: Abnormal vs normal karyotype was associated with older age (p=0.03), hemoglobin<10 g/dL (p=0.0009), white blood cell count (WBC) >15 x 109/L (p=0.02), absolute neutrophil count (ANC) >10 x 109/L (p=0.03), absolute lymphocyte count (ALC) >2.5 x109/L ( p=0.04), peripheral blood (PB) blast ≥1% (p<0.0001), bone marrow (BM) blast ≥10% (p<0.0001) and circulating immature myeloid cells (IMC) (p=0.0003). +8 (p=0.01), +21 (p=0.03) and der (3q) (p=0.03) were associated with hemoglobin <10 g/dL. -Y was associated with older age (p=0.04), lower PB (p=0.04) and BM (p=0.02) blasts. -7/7q was associated with leukocytosis (p=0.005), neutrophilia (p=0.04), and higher PB blasts (p=0.004). 20q- was associated with thrombocytopenia (p=0.04). Molecular correlates: ASXL1 mutations were associated with abnormal karyotype (p=0.04) and SRSF2 with normal karyotype (p=0.02). In comparison to other abnormal karyotypes, the incidence of ASXL1 mutations was lower in –Y (P=0.04) and der(3q) (p=0.03). U2AF1 mutations were associated with monosomal karyotype (p=0.03) and SF3B1 with der (3q) (p<0.0001). Prognostic relevance : Median follow-up was 1.8 years with 244 (60%) deaths and 79 leukemic transformations (19%). A step-wise survival analysis resulted in three distinct cytogenetic risk categories (Figure 1): high (complex and monosomal karyotype), intermediate (all abnormalities not in high or low risk) and low (normal, sole -Y and sole der (3q)); the corresponding median survivals were 0.2 (HR 8.1, 95% CI 4.6-14.2), 1.7 (HR 1.7, 95% CI 1.2-2.3). In multivariable analysis, the particular cytogenetic risk stratification remained significant in the context of Mayo molecular model (p<0.0001), MDAPS (p<0.0001), and the GFM risk model (P<0.0001). The Mayo-French cytogenetic risk model was also effective in predicting leukemic transformation with HR of 10.9 (95% CI 4.2-27.8) for high and 2.2 (95% CI 1.3-3.7) for intermediate risk groups. Conclusion: Cytogenetic abnormalities are seen in approximately 30% of patients with CMML and display significant associations with certain molecular and phenotypic characteristics. We describe a novel cytogenetic prognostic model for both over-all and leukemia free survival in CMML. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Cytogenetic and Molecular Profile Analysis in Hispanic Chronic Myelomonocytic Leukemia Patients From Puerto Rico

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqz121.005 ◽

2019 ◽

Vol 152 (Supplement_1) ◽

pp. S106-S106

Author(s):

Nawar Matti ◽

Ruifang Zheng ◽

Khalid Algarrahi ◽

Albert Alhatem ◽

Xinlai Sun ◽

...

Keyword(s):

Puerto Rico ◽

Incidence Rate ◽

Lower Incidence ◽

Patient Population ◽

Chronic Myelomonocytic Leukemia ◽

Wild Type ◽

Cytogenetic Abnormalities ◽

Molecular Profiles ◽

Lower Incidence Rate ◽

Myelomonocytic Leukemia

Abstract Objectives Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy with both myelodysplastic and myeloproliferative features. The clinical and pathological features of CMML are highly heterogeneous. It was reported that Hispanic whites had an age-adjusted lower incidence rate of CMML compared to non-Hispanic whites. The aim of this study is to define the cytogenetic and genomic landscape of Hispanic CMML patients and explore their potential clinical significance. Methods Clinically relevant cytogenetic results and 40-gene molecular profiles of Hispanic CMML patients in Puerto Rico (PR) from 2009 to 2018 were obtained retrospectively. Results Total 111 Hispanic CMML patients from PR were diagnosed in our institute from 2009 to 2018. The age range was from 46 to 96 years with a median age of 74. Sixty-five were male and 46 were female. The epidemiological features are similar to that in a general CMML patient population. In total, 107 patients had karyotypes available; 17 patients had abnormal karyotype (17/107, ~16%). Compared with general CMML patients, Hispanic CMML patients had a significantly lower rate of cytogenetic abnormalities (30% vs 16%). Among total 111 Hispanic CMML patients, 40-gene myeloid molecular profiles were performed in 56 CMML patients. Fifty-five out of 56 patients had mutations identified (~98.2%). The most frequent mutated genes were TET2, SRSF2, ASXL1, NRAS, and ZRSR2. Twenty-six of 56 patients (~46.4%) had mutated TET2/wild-type ASXL1. Previous studies indicated that mutated ASXL1, NRAS, RUNX1, and SETBP1 likely associate with an unfavorable prognosis in a general CMML patient population. Mutated TET2 with wild-type ASXL1 (muTET2/wtASXL1) may associate with a favorable prognosis. Compared with general CMML patients, Hispanic CMML patients in this study had relatively lower mutational rates in ASXL1 (30.4% vs 37.0%), NRAS (10.7% vs 11.7%), RUNX1 (5.3% vs 7.9%), and SETBP1 (5.3% vs 8.9%) and a higher rate of muTET2/wtASXL1 (46.4% vs 37.8%). Conclusion Hispanic CMML patients from PR had a significantly lower rate in cytogenetic abnormalities; relatively lower mutational rates in ASXL1, NRAS, RUNX1, and SETBP1; and a higher mutational rate in muTET2/wtASXL1. The findings raise a possibility of a better prognosis in Hispanic CMML patients and could be one of the explanations of a lower incidence rate of CMML in Hispanic population.

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MicroRNA Expression Profiles in Chronic Myelomonocytic Leukemia

Blood ◽

10.1182/blood.v112.11.2699.2699 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2699-2699

Author(s):

Mehdi Nassiri ◽

Joseph Olczyk ◽

Samantha Knapp ◽

Gail Vance ◽

Anupama Tewari ◽

...

Keyword(s):

Bone Marrow ◽

Mirna Expression ◽

Expression Profiles ◽

Chronic Myelomonocytic Leukemia ◽

Differentially Expressed ◽

Cytogenetic Abnormalities ◽

Normal Bone ◽

Normal Reference ◽

Mirna Expression Profiles ◽

Myelomonocytic Leukemia

Abstract Chronic myelomonocytic leukemia (CMML) is a hematopoietic malignancy with hybrid myeloproliferative and myelodysplastic features. The diagnostic criteria for CMML are evolving with the progress of our knowledge on various genetic lesions involved in the pathogenesis of myeloid neoplasms. This shift, including molecular genetic lesions in the diagnosis process, is highlighted in updated 2008 WHO classification system, which excludes myeloproliferative neoplasms with PDGFRB rearrangement, monocytosis and eosinophilia from CMML category. Despite these recent advancements, CMML remains a heterogeneous group of diseases with variable patient outcomes and no well-defined targeted therapy. To further investigate the biological diversity of this disorder, we studied microRNA (miRNA) expression profiles, their relation to the diagnostic and clinical parameters in CMML, and compared these profiles to global miRNA expression in normal reference bone marrow samples. MicroRNAs are a class of non-coding RNA molecules that alter gene expression by targeting and blocking mRNA. The role of miRNAs in carcinogenesis is related to their targeting of messenger RNAs encoding for oncogenes and tumor suppressor genes. Bone marrow samples from 22 patients with CMML were included in the study. Median age of the patients was 71 years with a range from 39 to 92 years. There were 15 males and 7 females. Seventeen patients presented with CMML-1 (blasts less than 5% in peripheral blood and less than 10% of bone marrow differential count). The remaining patients showed CMML-2. Nine patients had WBC below 13×109/L defining a myelodysplastic type of CMML. Cytogenetic results were available in 20 patients. Fourteen patients demonstrated a normal karyotype. Normal pooled bone marrow samples were used as a reference. The total RNA was isolated using RecoverAll RNA extraction kit. Micoroarray studies were performed using Agilent human miRNA microarrays (version 1.0) containing probes for 470 human and 64 human viral miRNAs cataloged in the Sanger database v9.1. The results were analyzed using BRB array tool and Genesis software. Unsupervised hierarchical clustering discovered two different groups of CMML samples with patterns of miRNA expression distinct from normal bone marrows (oneway ANOVA). Twenty seven miRNAs were differentially expressed in normal bone marrow reference samples vs. CMML-1 and -2. There was an overlap in miRNA profiles between groups of CMML based on blast percentage (CMML-1 vs. CMML-2), WBC count (<13×109/L vs. ≥13×109/L) and presence or absence of cytogenetic abnormalities. However, using PAM algorithm the following miRNAs showed predictive power: hsa-miR-519b (in CMML-1 vs. 2); hsa-miR-15b and hsa-miR-432* (in groups of samples separated by a cut-off WBC of 13×109/L) and hsa-miR-223 (comparing CMML with and without cytogenetic abnormalities). In summary, significantly different miRNA profiles were seen in CMML as compared to normal reference bone marrow. Two distinct subgroups of CMML were defined by the miRNA expression profiles. Select miRNAs were differentially expressed in known biological and clinical subgroups of CMML. Further correlation of clinical and outcome data with subgroups of CMML defined by miRNA expression profiles will be presented.

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Chronic Myelomonocytic Leukemia With Preexisting Myelodysplastic Syndrome Or Myeloproliferative Neoplasm: Two Stages Of One Disease With Poor Prognosis

Blood ◽

10.1182/blood.v122.21.1342.1342 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1342-1342 ◽

Cited By ~ 1

Author(s):

Yin Xu ◽

Aine Yung ◽

Brian Kwok ◽

Karen Macdonell ◽

Bashar Dabbas ◽

...

Keyword(s):

Myelodysplastic Syndrome ◽

De Novo ◽

Myeloproliferative Neoplasm ◽

Chronic Myelomonocytic Leukemia ◽

Chromosome Abnormalities ◽

Refractory Anemia ◽

Jak2 Mutation ◽

Cytogenetic Abnormalities ◽

Two Stages ◽

Myelomonocytic Leukemia

Abstract Introduction Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy characterized by persistent monocytosis with features of a myelodysplastic syndrome (MDS) and/or myeloproliferative neoplasm (MPN). While most cases present as de novo disease, a subset of CMML has been described in the literature to evolve from a preexisting MDS (MDS-CMML). CMML with preexisting MPN (MPN-CMML) has not been characterized to our knowledge. It is uncertain whether CMML patients with preexisting MDS or MPN have one or more disease processes and if such patients behave differently from patients who present with de novo CMML. In an attempt to address these questions, we compared the clinicopathologic features between groups of MDS-CMML, MPN-CMML, and de novo CMML in the present study. Methods 126 cases with newly diagnosed CMML were retrieved from our database over a 3-year period. 22 cases had preexisting MDS (n=15) or MPN (n=7). Prior diagnoses of MDS included refractory anemia (n=5), refractory anemia with ring sideroblasts (n=2), MDS with isolated 5q deletion (n=1), refractory cytopenia with multilineage dysplasia (n=6), and refractory anemia with excess blasts-1 (n=1). Prior diagnoses of MPN included essential thrombocythemia (n=1), primary myelofibrosis (n=3), and MPN NOS (n=3). Cytogenetic studies were performed in all cases. Other parameters obtained included age, gender, hemoglobin, white blood cell count, monocytes, platelets, bone marrow blasts and histology, and JAK2/MPL mutations. 22 consecutive cases of de novo CMML were included for comparative analysis. Results CMML with preexisting MDS or MPN comprised 17% of CMML (22/126 patients). Among these 22 patients, 15 were male and 7 female with a median age of 79 (range 61-86) years. Median age of the patients at CMML stage was similar to that of patients with de novo CMML (77 years; range 65-89). The median time between disease presentation as MDS or MPN and CMML was 22 months. Patients presented with marked monocytosis at the CMML stage (mean: 23% and 4564/uL) as compared to the stage of MDS (mean: 13% and 794/uL; p<0.001) or MPN (mean: 6.4% and 1216/uL; p<0.001); and the monocyte count was similar to that present in de novo CMML (mean: 24% and 4313/uL). Marrow blasts were significantly increased at the CMML stage as compared to the stage of MDS (mean: 5.3 vs. 1.6; p=0.017), MPN (mean: 5.1 vs. 1.9; p=0.048), or de novo CMML (5.2 vs. 1.9; p=0.009). There was no significant difference in average hemoglobin, platelet count or marrow cellularity between cases at the two disease stages or among the MDS-CMML and MPN-CMML subgroups. However, the marrows of MPN-CMML showed significantly increased diffuse reticulin fibrosis (p=0.002) and marked megakaryocytic hyperplasia (p=0.002) as compared to MDS-CMML. CMML with preexisting MDS or MPN is more frequently associated with cytogenetic abnormalities than de novo CMML (50% vs. 23%), although this difference did not reach statistical significance (p=0.116). 8 (36%) cases had chromosome abnormalities at the MDS or MPN stages; 7 (87%) of the 8 cases demonstrated persistent chromosome abnormalities at the CMML stage. In addition, 4 (18%) patients acquired chromosome abnormalities at the CMML stage. JAK2 mutation was seen in 1 (7%) of 15 cases of MDS-CMML and 4 (57%) of 7 cases of MPN-CMML. Notably, 2 cases of JAK2 positive MPN became JAK2 negative at the CMML stage; one of the patients had been previously treated with a JAK2 inhibitor. No MPL mutation was found in any case. Conclusions CMML with preexisting MDS or MPN is not uncommon. The majority of cases exhibit persistent chromosomal abnormalities from the preexisting MDS or MPN, supporting the notion of one disease with two stages of presentation. The findings of a higher frequency of cytogenetic abnormalities and occasional cytogenetic evolution may suggest that chromosome alteration is one of the mechanisms involved in triggering disease progression to CMML. JAK2 V617F was more frequent in MPN-CMML, which correlated with myelofibrosis and megakaryocytic hyperplasia. However, loss of JAK2 mutation can occur at CMML stage. Loss/inhibition of JAK2 activity may contribute to a change in disease course. Our study revealed that CMML with preexisting MDS or MPN is characterized by more advanced disease with increased marrow blasts and therefore may be associated with a poorer prognosis. Disclosures: No relevant conflicts of interest to declare.

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Prognostic impact of acquisition of cytogenetic abnormalities during the course of chronic myelomonocytic leukemia

American Journal of Hematology ◽

10.1002/ajh.24108 ◽

2015 ◽

Vol 90 (10) ◽

pp. 882-887 ◽

Cited By ~ 9

Author(s):

Guilin Tang ◽

Bing Fu ◽

Shimin Hu ◽

Xinyan Lu ◽

Zhenya Tang ◽

...

Keyword(s):

Chronic Myelomonocytic Leukemia ◽

Prognostic Impact ◽

Cytogenetic Abnormalities ◽

Myelomonocytic Leukemia

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Characterization of Cytogenetic Abnormalities and Mutations in ASXL1, SRSF2, CBL and JAK2 Genes in Chronic Myelomonocytic Leukemia

Blood ◽

10.1182/blood.v120.21.4809.4809 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4809-4809

Author(s):

Laura Palomo ◽

Blanca Xicoy ◽

Silvia Marce ◽

Olga Garcia ◽

Marta Cabezon ◽

...

Keyword(s):

Overall Survival ◽

Survival Analysis ◽

Prognostic Factor ◽

Cytogenetic Analysis ◽

Biological Data ◽

Chronic Myelomonocytic Leukemia ◽

Prognostic Impact ◽

Cytogenetic Abnormalities ◽

Exon 1 ◽

Myelomonocytic Leukemia

Abstract Abstract 4809 Introduction: Chronic myelomonocytic leukemia (CMML) is a clonal haematopoietic malignancy characterized by features from both myelodisplastic syndromes and myeloproloferative neoplasms. CMML median overall survival is 20 months and 15–30% of cases progress to acute myeloid leukemia (AML). Molecular biology of CMML is poorly understood. Clonal cytogenetic abnormalities are found in 20–30% of cases. Recently, some recurrent gene mutations have been reported. The most frequent mutated genes are TET2 (30–50%), ASXL1 (35–56%), SRSF2 (28–47%), RUNX1 (8–37%), CBL (10–22%) and K/NRAS (2–22%). We sought to characterize type, frequency and prognostic implication of cytogenetic alterations and genetic mutations (ASXL1, CBL, JAK2 and SRSF2) in a cohort of 20 patients with CMML. Methods: A retrospective study was performed on 20 CMML cases (11 CMML-1, 9 CMML-2) for whom clinical and biological data were available. Median age at diagnosis was 66 years (range: 49 – 84 years), with a male predominance of 1.9:1 and 42% frequency of progression to AML. Conventional cytogenetic analysis was performed in bone marrow (BM) samples obtained at diagnosis (n=19) and at progression to AML (n=8). For mutation analysis, DNA was extracted from BM samples at diagnosis (n= 20). Sanger sequencing was performed to study mutations in ASXL1 (exon 12), SRSF2 (exon 1) and CBL (exons 8 and 9) genes, while JAK2 V617F mutation was analyzed by endpoint genotyping. Survival analysis was performed using Kaplan-Meier estimate and log-rank tests were used for comparisons. The χ2 and Fisher's exact tests were used to analyze differences in the distribution of variables among patient subsets. Results: Aberrant karyotypes were seen in 5/19 (26%) cases at diagnosis and 6/8 (83%) cases at progression to AML. Alterations observed at diagnosis were typical from CMML (trisomy 8, 7q deletions and 12p structural alterations), while those observed at progression were more common in AML (Table 1). Heterozygous somatic ASXL1 mutations were detected in 8/19 (42%) cases. A total of 6 different mutations were seen in these 8 cases, being the recurrent mutation p.G646WfsX12 (g.76303dupG) the only one seen in more than one patient (4/8, 50%). In addition, 4 cases harboured two point mutations located at 3' of exon 12 (g.79017A>G and g.78128C>T). Somatic SRSF2 mutations were detected in 4/20 (20%) cases. All of them were heterozygous, missense mutations located at hotspot P95. In 3 cases P95 changed to P95H (g.535 C>A), while in 1 case it changed to P95L (g.535 C>T). In addition, 1 silence mutation was detected in 1 patient at the beginning of exon 1 (g.395 C>T) of SRSF2. No mutations were seen in CBL and JAK2 genes. ASXL1 and SRSF2 mutations did not correlate with either CMML-1/CMML-2 subtypes or myelodysplastic/myeloproliferative variants. Survival analysis revealed that the only adverse prognostic factor was CMML-2 subtype. Compared to CMML-1, patients with CMML-2 had worse overall survival (median OS at 2 years: 18% vs 21%, p=0.05) and progression-free survival (median PFS at 2 years: 21% vs 57%, p=0.002). Mutations in ASXL1 had no prognostic impact, while a trend towards higher PFS was seen in cases with SRSF2 mutations, although it was not statistically significant. Conclusions: Cytogenetic analysis revealed that the percentage of aberrant karyotypes in CMML increases considerably at progression to AML. Mutational analysis showed that ASXL1 and SRSF2 are frequently mutated in CMML. There are multiple ASXL1 mutations throughout the exon 12, while missense SRSF2 mutations located at the hotspot P95. CMML-2 is still the only prognostic factor associated to worse OS and PFS. Disclosures: No relevant conflicts of interest to declare.

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Monosomal Karyotype Predicts Adverse Prognosis In Patients With Chronic Myelomonocytic Leukemia

Blood ◽

10.1182/blood.v122.21.1334.1334 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1334-1334

Author(s):

Aysha K Alsahlawi ◽

Hassan Alkhateeb ◽

Mrinal M. Patnaik ◽

Kebede Begna ◽

Michelle Elliott ◽

...

Keyword(s):

Multivariate Analysis ◽

Chronic Myelomonocytic Leukemia ◽

Wilcoxon Test ◽

Cytogenetic Abnormality ◽

World Health ◽

Published Data ◽

Structural Abnormality ◽

Cytogenetic Abnormalities ◽

Myelomonocytic Leukemia ◽

Monosomal Karyotype

Abstract Background Chronic myelomonocytic leukemia (CMML) is a clonal hematologic disorder that was classified by the World Health Organization (WHO) as a myelodysplastic/ myeloproliferative overlap disease. Cytogenetic abnormalities have a significant prognostic role in many hematologic neoplasms, but their prognostic value in CMML has been debatable. Recently, monosomal karyotype (MK) has been reported to be a marker of poor prognosis in patients with myelodysplastic syndromes (MDS) and primary myelofibrosis, but its value in CMML is unknown. Aim To study MK effect on clinical outcome for patients diagnosed with CMML Method A retrospective study of all cases diagnosed with CMML at Mayo Clinic Rochester between 1994 to 2011 was performed. Only pts with complete cytogenetic analysis at presentation to our institution were included. MK was defined as the presence of ≥ 2 autosomal monosomies or one autosomal monosomy with at least one structural abnormality (Breems et al, JCO 2008). CK was defined as the presence of at least 3 chromosomal abnormalities. Appropriate IRB approval was obtained in accordance with Helsinki declaration. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V9. Results A total of 262 pts diagnosed with CMML had available cytogenetic data at diagnosis. Median age was 72 years, 176 (67%) were male. Median hemoglobin 10.5 g/dL, white blood cells (wbc) 12 x109/L, platelet 89 x109/L, peripheral blood (PB) blast 0, and bone marrow (BM) blast 4%. CMML2 was seen in 9% while 47% were proliferative (wbc >13). Leukemic transformation was documented in 34 pts (13%). Median overall survival was 513 days. Cytogenetic (CG) analysis was diploid in 167 pts (64%). Trisomy 8 was the most frequent cytogenetic abnormality at 8% (22), followed by complex karyotype (CK) 5% (14), then -7 at 4% (10) and MK 3% (7, six of which were also CK). Comparing pts with diploid CG to other categories indicates: to abnormal CG pts had lower wbc (0.001), PB blasts (p<0.0001), and BM blasts (p=0.0001); to CK pts had lower PB blasts (p=0.003) and higher platelets (p=0.03); to -7 pts had lower wbc (p=0.005), PB blast (p=0.0004), BM blasts (p=0.03) and higher platelets (p=0.03); to +8 pts had lower PB blast (p=0.02) and BM blasts (p= 0.01); no difference was noted when compared to MK. Median OS was statistically significantly worse in MK+ vs MK- (24 vs 527 days, p= 0.002), but not in other comparisons: -7 vs others (250 vs 527 days, p=0.2), CK+ vs CK- (256 vs 527 days, p=0.05), diploid vs others (570 vs 365 days, p=0.1), +8 vs others (312 vs 527 days, p=0.1). Pts with MK+ only or MK+CK+ did worse than CK+ only or other groups (4, 63, 304, 527 days, respectively, p<0.0001). On a multivariate analysis, MK+ (in addition to platelet, BM blast, hemoglobin, and wbc) did have an impact on OS (p=0.0004), while CK+, -7, +8, diploid CG, age, PB blast did not. Conclusion Cytogenetic abnormalities were not frequent findings in pts diagnosed with CMML (36%), but did affect wbc, PB and BM blasts. The most common cytogenetic abnormality was +8 while MK was present at 3% (less than published data in MDS). Only MK predicted statistically significant shorter mOS between all other cytogenetic categories on both univariate and multivariate analysis. This finding needs to be validated by larger cohorts of pts due to its rare occurrence in CMML. Disclosures: No relevant conflicts of interest to declare.

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