• bone marrow;
  • cytogenetics;
  • karyotype;
  • myelofibrosis with myeloid metaplasia;
  • myeloid disorders


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

The prognostic significance of bone marrow cytogenetic lesions in myelofibrosis with myeloid metaplasia (MMM) was investigated in a retrospective series of 165 patients. An abnormal karyotype was demonstrated in 57% of patients. At diagnosis (n = 92), 48% of the patients had detectable cytogenetic abnormalities, and clonal evolution was frequently demonstrated in sequential studies. More than 90% of the anomalies were represented by 20q–, 13q–, +8, +9, 12p–, and abnormalities of chromosomes 1 and 7. Of these, 20q–, 13q– and +8 were the most frequent sole abnormalities, each occurring in 15–25% of the abnormal cases. Trisomy 9 and abnormalities of chromosomes 1 and 7 were equally prevalent but were usually associated with additional cytogenetic lesions. Chromosome 5 abnormalities were infrequent but were over-represented in the group of patients exposed to genotoxic therapy. In a multivariate analysis that incorporated other clinical and laboratory variables, the presence of an abnormal karyotype did not carry an adverse prognosis. Instead, +8, 12p–, advanced age and anaemia were independent prognostic determinants of inferior survival. In particular, survival was not adversely affected by the presence of either 20q– or 13q–.

Bone marrow karyotype analysis is an integral part of diagnostics in myeloid disorders. The detection of a consistent cytogenetic abnormality is not only diagnostically useful (Nowell & Hungerford, 1960; Larson et al, 1984) but also provides a direction in pathogenetic studies (Daley et al, 1990; de The et al, 1990) that may result in rational therapy (Huang et al, 1988; Druker & Lydon, 2000). The majority of myeloid disorders do not bear a specific karyotypic marker and observed abnormalities may not always represent primary pathogenetic events (Dewald & Wright, 1995). Furthermore, cytogenetically detectable ‘subclones’ may arise because of genetic instability and may or may not participate in disease progression (Lowenberg et al, 1982; Tamura et al, 1993). In any case, the presence of characteristic patterns of non-random chromosomal changes may still be pathogenetically essential, and these patterns have also been used for diagnostic, prognostic and treatment purposes. Compared with acute myeloid leukaemia (Grimwade et al, 1998) and the myelodysplastic syndromes (Greenberg et al, 1997; Sole et al, 2000), karyotypic information has been under-utilized in the diagnosis and prognosis of patients with chronic myeloproliferative diseases.

Myelofibrosis with myeloid metaplasia (MMM) encompasses agnogenic (AMM), post-polycythaemic (PPMM) and post-thrombocythaemic (PTMM) myeloid metaplasia. AMM is currently classified with essential thrombocythaemia and polycythaemia vera as a chronic myeloproliferative disease and is characterized by a myelophthisic anaemia, hepatosplenomegaly from extramedullary haematopoiesis, and dysplastic megakaryocytic hyperplasia that is associated with bone marrow fibrosis (Tefferi, 2000). PPMM and PTMM develop in 10–20% of patients with polycythaemia vera (Berk et al, 1995; Najean & Rain, 1997) and in 5% of patients with essential thrombocythaemia (Tefferi et al, 2001) respectively. At present, treatment in MMM is mainly palliative, with only a minority of young patients being eligible for ‘curative’ therapy with allogeneic haematopoietic stem cell transplantation (Guardiola et al, 1999). Patients with anaemia may derive transient benefit from the use of androgen preparations (Besa et al, 1982), while cytoreductive treatment is used to control organomegaly and peripheral leucocytosis and thrombocytosis (Manoharan, 1991; Gilbert, 1998). Most patients ultimately require therapeutic splenectomy for the alleviation of mechanical and hypercatabolic symptoms, portal hypertension and refractory anaemia (Tefferi et al, 2000).

Current evidence supports the progenitor cell origin of clonal myeloproliferation and the polyclonal nature of bone marrow stromal cells in MMM (Jacobson et al, 1978; Wang et al, 1992). In addition, aberrant expression of fibrogenic and angiogenic cytokines, and marked increases in bone marrow collagen fibrosis, new bone formation, and microvessel density, have been demonstrated (Martyre et al, 1994; Reilly, 1994; Mesa et al, 2000). However, the underlying molecular lesions for these processes remain elusive. An extensive cytogenetic study in MMM, in view of the definitional inclusion of patients with AMM, PPMM and PTMM, may provide important pathogenetic clues that may be linked to the various aspects of the disease process. Furthermore, this information may complement morphological distinction from other myeloid disorders (Werner et al, 1995) and supplement current prognostic models (Dupriez et al, 1996; Reilly et al, 1997; Cervantes et al, 1998) that are utilized in the selection of appropriate candidates for risk-adjusted treatment strategies (Guardiola et al, 1999).

Patients and methods

  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

After approval by the institutional review board, clinical and laboratory databases spanning 20 years were systematically searched for patients with a diagnosis of MMM whose bone marrow and cytogenetic studies were available for analysis. The study population included patients with cytogenetic information either at diagnosis or some time during the course of the disease. Diagnosis of MMM was made according to conventional criteria and included AMM, PPMM and PTMM (Barosi et al, 1999). Cases of myelodysplastic syndrome with myelofibrosis, acute myelofibrosis and atypical chronic myeloid disorder were excluded (Dickstein & Vardiman, 1995). In each case, bone marrow morphology was re-reviewed with an emphasis on cases having infrequent cytogenetic markers. Leukaemic transformation was confirmed by demonstration of more than 30% blasts in the bone marrow. Both the direct technique and unstimulated 24-h culture were used to harvest 20 metaphases, whenever possible, in all bone marrow specimens (Dewald et al, 1985).

Descriptive and statistically analysed data, both at diagnosis and at the time of cytogenetic studies, were obtained from the entire cohort of patients. Survival analysis and clinical correlations were considered from the time of karyotype analysis for the entire cohort and from the time of diagnosis for patients who had cytogenetic studies performed at diagnosis (± 4 months). Variables examined included clinical features that were reportedly considered to have prognostic value. Because of incomplete or poor documentation in some patients, the presence or absence of constitutional symptoms was not recorded. The Dupriez prognostic score allocation was as previously published (Dupriez et al, 1996). Overall survival was defined as the interval from diagnosis to death or last contact. An event was defined as a death from any cause unless otherwise indicated. Various univariate techniques were applied, including Fisher's exact test for categorical variables and the Kruskal–Wallis and Wilcoxon rank-sum tests for continuous variables. The results were subsequently evaluated by multivariate analysis. A Cox proportional hazards regression analysis was used to assess the prognostic relevance of several clinical and pathological variables. All data were analysed using SAS software (SAS, Cary, NC, USA).


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

Patient groups

Of the entire cohort of 165 patients, 76 were women and the median age at diagnosis was 62 years (28–92 years). One hundred and twelve patients (68%) had AMM, 29 (18%) had PPMM and 24 (14%) had PTMM. The median follow-up period was 44 months (range 0–475 months) from diagnosis and 16 months (range 0·1–114 months) from the time of karyotype analysis. Initial karyotype analysis was performed at a median of 8·1 months (range 0–385 months) from diagnosis. Ninety-two patients (56%) had karyotypic analysis at diagnosis (± 4 months) and, of these, 83 were chemotherapy naive at the time and 61 had AMM. Overall, 132 patients (80%) were chemotherapy naive at the time of karyotype analysis and 33 (20%) had received genotoxic treatment. Forty-three patients had multiple (two or more) cytogenetic studies during their clinical course. The number of metaphases available for analysis was similar in all study subgroups (median 20, range 5–30).

Cytogenetic findings

The prevalence of an abnormal karyotype in the entire cohort of 165 patients with MMM was 57% and did not differ significantly among the three subtypes of MMM (AMM 55%, PPMM 62%, PTMM 42%). At diagnosis, the incidence was 48% for MMM (n = 92) and 49% for AMM (n = 61). The likelihood of detecting a cytogenetic clone increased with time (73%), even in the absence of exposure to genotoxic agents (Table I). This observation was consistent with the higher degree of chimaerism observed in the patients with delayed cytogenetic studies (Table I). In cytogenetically abnormal cases, the majority in all the subgroups were represented by a single clone, and previous exposure to chemotherapy may have contributed to the development of cytogenetic subclones but not to the appearance of new clones (Table I).

Table I.  Incidence and complexity of cytogenetic abnormalities in 165 patients with myelofibrosis with myeloid metaplasia.
ParameterAll patients (n = 165)Chemotherapy-naive patients (n = 132)Chemotherapy-exposed patients (n = 33)Karyotype done at diagnosis* (n = 83)Karyotype done after diagnosis* (n = 49)
  • *

    Karyotype analysis was performed in both previously untreated (132) and chemotherapy-treated (33) patients. In chemotherapy-naive patients, the cytogenetic study was performed either at diagnosis (83 patients) or some time after diagnosis (49 patients).

  •   †Number of abnormal clones refers to mutually exclusive cytogenetic clones.

  •   ‡Number of cytogenetic abnormalities refers to all detectable numeric or structural lesions.

  •   AN, presence of both normal and abnormal metaphases; AA, all metaphases abnormal.

 Normal71 (43%)56 (42%)15 (46%)43 (52%)13 (27%)
 Abnormal94 (57%)76 (58%)18 (55%)40 (48%)36 (73%)
 AN51 (31%)43 (33%)8 (24%)21 (25%)22 (45%)
 AA43 (26%)33 (25%)10 (30%)19 (23%)14 (28%)
Number of abnormal clones
 168 (72%)55 (73%)13 (72%)31 (78%)24 (67%)
 geqslant R: gt-or-equal, slanted 226 (28%)21 (27%)5 (28%)9 (22%)12 (33%)
Number of cytogenetic abnormalities
 151 (54%)45 (59%)6 (33%)23 (58%)22 (61%)
 216 (17%)13 (17%)3 (17%)4 (10%)9 (25%)
 geqslant R: gt-or-equal, slanted 327 (29%)18 (24%)9 (50%)13 (33%)5 (14%)

Table II provides a detailed account of the particular cytogenetic lesions. The most frequent anomalies were 20q–, 13q–, +8, +9, and abnormalities of chromosomes 1 and 7, each representing 10–25% of the abnormal cases. Abnormalities of chromosomes 5 and 12 were somewhat less frequent. In general, the pattern of chromosomal changes was similar between the entire cohort of 165 patients with MMM and the subset of 83 chemotherapy-naive patients with karyotype information at diagnosis (Table II). In both groups, a little more than half the abnormal cases constituted a simple cytogenetic lesion, and abnormalities of chromosomes 1, 5, 7 and 9 were almost always associated with other chromosomal changes. This suggested that the particular lesions represented a cytogenetic subclone and, thus, a secondary event. Furthermore, abnormalities of chromosome 5 were overrepresented in chemotherapy-exposed patients (29% of the abnormal cases), suggesting a characteristic treatment-induced event.

Table II.  Specific details of karyotypic abnormalities in 165 patients with myelofibrosis with myeloid metaplasia and a subset of 83 chemotherapy-naive patients who were studied at diagnosis.
 All patients (n = 165) Abnormal cases = 94 (57%)Chemotherapy-naive patients at diagnosis (n = 83) Abnormal cases = 40 (48%)
Karyotype abnormalitySimple lesions* (n = 51)Complex lesions (n = 43)All lesions (n = 94)Simple lesions* (n = 23)Complex lesions (n = 17)All lesions (n = 40)
  • *

    Simple lesions refers to the presence of only one numeric or structural lesion.

  •   †Complex lesions refers to the presence of two or more numeric or structural lesions.

20q–11 (22%)9 (21%)20 (21%)6 (26%)2 (12%)8 (20%)
13q–11 (22%)8 (19%)19 (20%)3 (13%)3 (18%)6 (15%)
Abnormal chrom 1016 (37%)16 (17%)07 (41%)7 (18%)
+87 (14%)7 (16%)14 (15%)6 (26%)3 (18%)9 (23%)
+9111 (26%)12 (13%)07 (41%)7 (18%)
Abnormal chrom 124 (8%)4 (9%)8 (9%)112
−7/7q–3 (6%)7 (16%)10 (11%)06 (35%)6 (15%)
−5/5q–06 (14%)6 (6%)03 (18%)3 (8%)

The aforementioned cytogenetic pattern also characterized AMM (at diagnosis or otherwise), PPMM and PTMM (Table III). The corresponding incidence values were also similar, with the notable absence of a chromosome 1 abnormality in PTMM. In general, 20q–, 13q– and +8 were the most frequent simple cytogenetic lesions (each occurring in 15–25% of abnormal cases) (Table II). This was also true for AMM, PPMM and PTMM. The chromosomal breakpoint boundaries, involving 20q– and 13q–, were also similar among the three subtypes of MMM and included the q11.2–13·1 area for chromosome 20 and the q12–22 area for chromosome 13. Age, duration of disease or exposure to chemotherapy did not appear to alter the general pattern of either the gross chromosomal abnormalities or the precise breakpoint regions. Furthermore, examination of all cases with complex cytogenetic abnormalities that involved 13q– or 20q– revealed that both occurred as the primary cytogenetic clone, except in the presence of +8.

Table III.  Summary of three large cytogenetic series in agnogenic myeloid metaplasia and a comparative outline of chromosomal changes in post-polycythaemic (PPMM) and post-thrombocythaemic (PTMM) myeloid metaplasia.
   n (% abnormal cases)
StudynAA/AN (%)13q–/−1320q–1 abnl+87q–/−7+912 abnl5q–/−5+21/21p+
  • *

    Current study.

  •   †At diagnosis.

  •   AA, all metaphases abnormal; AN, presence of both normal and abnormal metaphases; abnl, abnormality.

Tefferi et al (2001)*112621412101088730
Reilly et al (1997)10637987451110
Demory et al (1988)4715461110013

Sequential cytogenetic studies were available in 43 patients. The median period between two consecutive studies was 19 months (range 43–114 months). A change in karyotype was documented in 20 patients (47%), eight of whom had a normal initial cytogenetic study. The new changes consisted of additional abnormalities in 15 patients, disappearance of an abnormality in four patients and a change of abnormality in one patient. The development of new cytogenetic abnormalities in the 20 patients was preceded by no specific therapy in two cases, treatment with hydroxyurea in 12 cases and treatment with anagrelide in five cases. Cytogenetic studies at the time of leukaemic transformation were not consistently available in the patients with transformation into acute leukaemia during the study period (20 patients).

Survival and follow-up information

Seventy-four of the total study population (n = 165) have died; the median follow-up period of the 91 patients who remain alive was 38 months (range 0–476 months) from diagnosis and 17 months (range 0–114) from the time of karyotype analysis. In the subgroup of patients who had their cytogenetic studies performed at diagnosis (n = 92), 58 are currently alive at a median follow-up of 19 months (range 0–113 months). The median survival from diagnosis was 79 months (range 0–476 months) for the entire cohort of 165 patients and 66 months (range 0–120 months) for the 92 patients with initial cytogenetic studies that were performed at the time of diagnosis. These values are largely similar to those reported by others and confirm the representative nature of our patient population.

Prognostic relevance of cytogenetic findings

Cytogenetic abnormalities and several other clinical and laboratory variables were examined for their prognostic significance by both univariate and multivariate statistical methods. Because karyotype analysis was not always available at the time of diagnosis, its prognostic value for ‘survival from diagnosis’ was considered only in those patients whose cytogenetic studies were performed at the time of diagnosis (n = 92) (Table IV). However, the entire cohort of patients with MMM (n = 165) was considered in the analysis of ‘survival from the time of karyotype studies’(Table IV). In a univariate analysis, advanced age, anaemia and the presence of either +8 or 12p– were significantly associated with shortened survival, both from diagnosis (n = 92) and from the time of karyotype analysis (n = 165) (Table IV). These variables, but no others, maintained their prognostic significance in a multivariate analysis.

Table IV.  Prognostic parameters of survival in 165 patients with myelofibrosis with myeloid metaplasia (MMM) and the subsets of 92 patients with MMM whose cytogenetic studies were done at the time of diagnosis.
 Prognostic significance for survival (P-values)
 Entire cohort (n = 165)  
ParameterSurvival from karyotypic analysisMMM at diagnosis (n = 92)
  1. *Dupriez prognostic score (Dupriez et al, 1996).

  2.   P-values that were statistically significant are given in bold type.

 Age (< 60 versus geqslant R: gt-or-equal, slanted 60 years)0·00010·001
 Type of MMM0·250·56
 Haemoglobin (< 10 versus geqslant R: gt-or-equal, slanted 10 g/dl)0·0020·008
 Leucocyte count0·270·60
 Platelet count0·740·97
 % blasts0·0040·12
 Dupriez score*0·190·31
 Spleen size0·070·51
 Normal versus abnormal0·080·06
 Simple versus complex0·240·19
 Abnormal 10·790·41
 Abnormal 120·0060·006

The negative survival trend associated with the mere presence of an abnormal karyotype in a univariate analysis (Table IV) was lost during a multivariate analysis. This particular observation suggested that the previously recognized association between abnormal cytogenetics and shortened survival in MMM may have been a result of the presence or absence of specific chromosomal changes, including +8 and 12p–. The differential effect on survival of specific chromosomal abnormalities is further depicted in Figs 1 and 2. Subsequently, we investigated the influence of the age-independent poor-risk factors (+8, 12p–, anaemia) on the survival of patients less than 60 years of age. Survival at 10 years from diagnosis was 56% for the good-risk group compared with 34% in the poor-risk category. The respective percentage survival at 6 years from the time of karyotype analysis was 60% and 33%.


Figure 1. Survival curves from diagnosis in mutually exclusive cytogenetic groups of patients with myelofibrosis with myeloid metaplasia.

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Figure 2. Survival curves from the time of karyotype analysis in mutually exclusive cytogenetic groups of patients with myelofibrosis with myeloid metaplasia.

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Twenty patients transformed into acute leukaemia during the study period. The pretransformation incidence of an abnormal karyotype in these 20 patients was 70%. Eleven of the 14 abnormal cases (79%) had two or more abnormalities. The proportion of patients with 13q–, 20q–, +8, +9, chromosome 1 abnormality, 12p–, and abnormalities of chromosome 7 and 5 who transformed into acute leukaemia was 0%, 10%, 21%, 17%, 19%, 25%, 30% and 50% respectively. Because of the small number of patients and events in each category, the observed differences were not statistically significant.


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References

Our findings in AMM (112 patients) were remarkably similar to those of the two largest cytogenetic series (a combined group of 153 patients) of newly diagnosed cases with AMM (Table III) (Demory et al, 1988; Reilly et al, 1997). All three studies, and a literature review of 157 abnormal cases (Bench et al, 1998), revealed that 13q–, 20q–, +8, and abnormalities of chromosome 1, 7 and 9 constitute more than 80% of the chromosomal changes in AMM as well as in MMM. The current study further demonstrates that a similar set of karyotypic lesions characterizes both PPMM and PTMM (Table III). Although the aforementioned characteristic lesions are also seen in polycythaemia vera (Bench et al, 1998), only 13–17% of patients with polycythaemia vera carry detectable cytogenetic clones at diagnosis, which consist primarily of complete or partial +9 and +8 (Rege-Cambrin et al, 1987; Swolin et al, 1988; Diez-Martin et al, 1991). Furthermore, 13q– and 20q– anomalies in polycythaemia vera are infrequently detected at diagnosis but their incidence increases with longer duration of disease, and the presence of 13q– has been loosely linked to imminent myelofibrosis (Rege-Cambrin et al, 1987; Swolin et al, 1988). Taken together, these observations suggest a potential link between some of the cytogenetic markers and the disease phenotype in MMM.

In the current study, only 20q–, 13q– and +8 were seen as single lesions, and abnormalities of chromosomes 1, 5, 7 and 9 were almost always associated with additional co-existing lesions. This suggests that the latter abnormalities represent cytogenetic subclones indicative of genomic instability, while the former abnormalities may represent primary events that are pathogenetically relevant. Although the aforementioned macrodeletions may be evidence for a critical regional mutation, it is equally conceivable that these cytogenetically ‘primary’ abnormalities are molecularly ‘secondary’ and have an impact on disease progression rather than on disease initiation. This contention is further supported by our demonstration of a time-dependent increase in both the detection rate of an abnormal karyotype and the percentage of abnormal metaphases. However, because the initial studies were not always done at diagnosis, this particular finding may reflect a selection bias in favour of clinically aggressive disease that may have resulted in the pursuit of a cytogenetic study. In any case, of the most frequent sole abnormalities we observed, 13q– is known to be associated more with MMM than with essential thrombocythaemia, early polycythaemia vera or myelodysplastic syndrome (Pastore et al, 1995). For example, in a series of 640 patients with myelodysplastic syndrome, a single abnormality of 13q– was encountered in only four patients (Sole et al, 2000). On the other hand, 20q– and +8 are frequently encountered in myelodysplastic syndrome, even as sole abnormalities (Perkins et al, 1997). Therefore, in the context of myeloid disorders, 13q– anomaly may be pathogenetically more relevant in MMM.

Loss of chromosome 13q material in our patients with MMM was always interstitial, with breakpoints at either 13q12 and 13q14 (13 cases) or 13q12 and 13q22 (six cases), and no significant difference among AMM, PPMM and PTMM. Similarly, the commonly deleted chromosome 13 region in the two other large cytogenetic studies in AMM (Demory et al, 1988; Reilly et al, 1997) and in other myeloid malignancies (Johnson et al, 1985; Sole et al, 2000) included the retinoblastoma gene (RB1) region (13q14), and the pattern of the breakpoints was not consistently different among the various subgroups of myeloid malignancies. Molecular characterization of 13q– in myeloid disorders has identified a commonly deleted region between bands q13.3 and q14.3 (La Starza et al, 1998). Fluorescence in situ hybridization studies of 13q translocations have revealed microdeletions that subsequently narrowed the minimal consensus deletion to the region that corresponded to the RB1 locus and its immediate neighbours (La Starza et al, 1998; Tanaka et al, 1999). Interestingly, similar monoallelic deletions characterize the 13q abnormalities in chronic lymphocytic leukaemia (Tanaka et al, 1999), multiple myeloma (Zojer et al, 2000) and other lymphoid malignancies (Wada et al, 1999). These observations suggest disease-specific functionality of a common 13q structural defect that is further illustrated by the different prognostic impact it has on chronic lymphocytic leukaemia (good prognosis) (Juliusson & Merup, 1998) and multiple myeloma (poor prognosis) (Zojer et al, 2000). In both the lymphoid and the myeloid disorders, alterations of the non-deleted RB1 allele are unusual (Pastore et al, 1995; La Starza et al, 1998).

One of the popular prognostic models in AMM considers haemoglobin level and leucocyte count to stratify patients into low-risk (median survival 93 months), intermediate-risk (median survival 26 months) and high-risk (median survival 13 months) groups (Dupriez et al, 1996). Others have shown the additional prognostic relevance of age (Cervantes et al, 1997), constitutional symptoms (Cervantes et al, 1998), peripheral blood granulocyte immaturity (Kvasnicka et al, 1997), bone marrow microvessel density (Mesa et al, 2000) and cytogenetic findings (Demory et al, 1988; Reilly et al, 1997). In one prognostic model that incorporated cytogenetic information, the median survival of patients below the age of 69 years who did not have either anaemia (haemoglobin leqslant R: less-than-or-eq, slant 10 g/dl) or abnormal karyotype was 180 months, compared with 22 months for the age-matched cohort with both anaemia and an abnormal karyotype (Reilly et al, 1997). However, a more recent study of young patients (< 56 years old) with AMM found current prognostic models to be less than adequate and did not confirm the prognostic value of chromosomal abnormalities (Cervantes et al, 1998). The results from the current study suggest that the presence or absence of specific clones (+8, 12p–) rather than an abnormal karyotype per se was prognostically important in MMM.

The demonstrated adverse prognostic property of +8 in MMM is consistent with previous observations that link +8 with poor prognosis in other myeloid disorders, including acute myeloid leukaemia (Schoch et al, 1997; Byrd et al, 1998) and myelodysplastic syndrome (Sole et al, 2000). On the other hand, the prognostic significance of 12p– in other myeloid disorders is less clear [United Kingdom Cancer Cytogenetics Group (UKCCG), 1992; Sole et al, 2000]. However, the reported association between 12p– and acute myeloid leukaemia with antecedent myelodysplastic syndrome (Streubel et al, 1998) suggests a biological link between myelodysplastic syndrome and MMM with a 12p– abnormality. This, in turn, might explain the observed inferior survival in patients with MMM and the specific cytogenetic abnormality. Although the small number of patients with chromosome 5 abnormality (six cases) did not allow valid statistical comparison, it was interesting that 50% of the patients with this particular cytogenetic lesion had transformation into acute leukaemia compared with 0% with 13q– (19 cases) and 10% with 20q– (20 cases) anomalies. The lack of an adverse prognosis associated with 20q– has previously been suggested in chronic myeloproliferative disorders (Campbell & Garson, 1994) and was also demonstrated in myelodysplastic syndrome (Greenberg et al, 1997). Because +8, 20q– and 13q– are the most frequent cytogenetic findings in patients with MMM, it is important to appreciate the dissimilar prognostic information they carry.


  1. Top of page
  2. Abstract
  3. Patients and methods
  4. Results
  5. Discussion
  6. References
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