Chronic myeloproliferative disorders and acute myeloid leukemia

9 patients diagnosed with myeloid malignancies (6 males and 3 females) aged 27 to 73 years (median 50 years); among them there 5 acute myeloid leukemia (AML) cases, not associated with a particular leukemia subtype: 1 acute monoblastic leukemia (AML-M5) (Akiyoshi et al., 1991), 1 acute myeloblastic leukemia with maturation (AML-M2) (Wan et al., 2002), 1 acute myeloblastic leukemia with minimal differentiation (AML-M0) (Dicker et al., 2007) and 2 cases of childhood AML (Raimondi et al 1999). 4 patients had various disorders: 1 secondary myelodysplastic syndrome (MDS) developed after chemotherapy for Hodgkins disease (Pedersen-Bjergaard et al 1997), 1 chronic neutrophilic leukemia (Yamamoto et al., 2002), 1 bilineage or biphenotypic leukemia (Tsutsumi et al., 2005) and 1 chronic myeloid leukemia patient who developed trisomy 8 /trisomy X abnormalities in Philadelphia-negative cells during imatinib mesylate treatment (Kim et al., 2008) (Table 1). Extra chromosome X was also reported in 2 patients receiving high dose chemotherapy who developed blood cytopenias as well as subtle to mild dysplastic features after autologous stem cell transplantation, which were not classifiable as MDS (Martinez-Climent et al., 2000)
Table 1. Clinical and karyotypic data of patients with myeloid malignancies and +X solely.

	Sex/Age	Diagnosis	Karyotype
1	F	Acute monoblastic leukemia	47,XX,+X
2	M/27	Refractory anemia previous chemotherapy for Hodgkins disease	47,XX,+X
3	M	Acute myeloid leukemia	47,XY,+X
4	M	Acute myeloid leukemia	47,XY,+X
5	F/58	Nonneoplastic hematologic disorder/lesion chemotherapy for adenocarcinoma	47,XX,+X      transient
6	F/43	Nonneoplastic hematologic disorder/lesion chemotherapy for  adenocarcinoma	47,XX,+X      transient
7	M/73	Chronic neutrophilic leukemia	47,XY,+X       at progression
8	F/44	Acute myeloblastic leukemia with maturation	47,XX,+X
9	M/67	Bilineage or biphenotypic leukemia	47,XY,+X
10	M	Acute myeloblastic leukemia with minimal differentiation	55,XY,+X,+4,+5,+8,+10,+13,+14,+17,+18/47,XY,+X
11	F/50	Chronic myeloid leukemia	47,XX,+8 47,XX,+X transient

Abbreviations: M, male; F, female.
1. Akiyoshi et al, 1991; 2. Pedersen-Bjergaard et al., 1997; 3. Raimondi et al., 1999; 4. Raimondi et al., 1999; 5. Martinez-Climent et al., 2000; 6. Martinez-Climent et al., 2000; 7. Yamamoto et al., 2002; 8. Wan et al., 2002; 9. Tsutsumi et al., 2005; 10. Dicker et al., 2007; 11. Kim et al., 2008.

Unknown, due to few number of patients and limited clinical data; the case with a secondary MDS, which developed 4 months after autologous stem cell transplantation for Hodgkins lymphoma died 2 months after the onset of MDS (Pedersen-Bjergaard et al.,1997). The 44-year-old woman with acute myeloblastic leukemia with maturation and abnormal eosinophils in the bone marrow developed diffuse alveolar damage and pulmonary hemorrhage while on induction chemotherapy and died 9 days after institution of chemetherapy (Wan et al., 2002). The 73-year-old man with chronic neutrophilic leukemia had normal karyotype at diagnosis, but after therapy with hydroxyurea for 7 months, the disease progressed to a blast crisis accompanied by appearance of an extra X chromosome, suggesting its role in the progression from chronic phase to the blast crisis of CNL (Yamamoto et al 2002). The 50-years old female with chronic myeloid leukemia developed only transient trisomy X in Philadelphia-negative cells during imatinib mesylate treatment (Kim et al., 2008).

The observation of an extra chromosome X may indicate constitutional or acquired anomaly, therefore it should be carefully interpreted when an extra X chromosome is the only abnormality or present in a form of chromosomal mosaicism in patients with hematologic malignancy.

An extra X chromosome as a sole acquired abnormality has been reported in patients with several hematologic malignancies especially in childhood acute lymphoblastic leukemia and lymphomas. While whole chromosome gains are frequent cytogenetic aberrations in myeloid malignancies, gain of X chromosome as the sole anomaly has been only occasionally observed. Its occurrence in both chronic and acute myeloid malignancies suggest involvement of multiple hematopoietic lineages. The presence of an additional copy of chromosome X might result in increased gene dosage and altered expression of many genes simultaneously, some of which could promote oncogenesis while others could perform inhibitory roles. The oncogenic mechanisms underlying remain largely elusive and it is unclear if gain of X chromosome directly contributes to malignant transformation or aneuploidy-induced transcriptional changes might only allow direct acquisition of cancer-driving mutations.