BCR rearrangement-negative chronic myelogenous leukemia revisited.
OBJECTIVE
To document the characteristics of patients with major breakpoint cluster region (M-bcr) rearrangement-negative chronic myelogenous leukemia (CML).


METHODS
The hematopathologist, who was blinded to patients' molecular status, reviewed the referral bone marrows and peripheral-blood smears from 26 patients with Philadelphia (Ph) translocation-negative CML who lacked Bcr rearrangement (and other evidence of a Bcr-Abl anomaly) and 14 patients (controls) with chronic-phase Ph-positive CML. Clinical data was ascertained by chart review.


RESULTS
Among the 26 M-bcr rearrangement-negative CML patients, three pathologic subtypes emerged: (1) patients indistinguishable from classic CML (n = 9), (2) patients with atypical CML (n = 8), and (3) patients with chronic neutrophilic leukemia (n = 9). Among the 14 patients with Ph-positive CML who were included in the blinded review, 13 were classified as classic CML, and one was classified as atypical CML. The only statistically significant difference between M-bcr rearrangement-negative subgroups was in the proportion of patients having karyotypic abnormalities, an observation common only in patients with atypical CML (P = 0.008). However, the small number of patients in each subgroup limited our ability to differentiate between them. Interferon alfa induced complete hematologic remission in five of 14 patients; four of these remissions lasted more than 5 years. Only one of 26 patients developed blast crisis. The median survival of the 26 patients was 37 months.


CONCLUSIONS
Patients with M-bcr rearrangement-negative CML fall into three morphologic subgroups. Disease evolution does not generally involve blastic transformation. Instead, patients show progressive organomegaly, leukocytosis, anemia, and thrombocytosis. Some patients in each subgroup can respond to interferon alfa.
Kurzrock
R
R
Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Bueso-Ramos
C E
CE
Kantarjian
H
H
Freireich
E
E
Tucker
S L
SL
Siciliano
M
M
Pilat
S
S
Talpaz
M
M
D000328:Adult; D000368:Aged; D000740:Anemia / Q000209:etiology; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018450:Disease Progression; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000150:complications / Q000235:genetics* / Q000473:pathology; D007964:Leukocytosis / Q000209:etiology; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D015513:Oncogene Proteins / Q000235:genetics*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D051562:Proto-Oncogene Proteins c-bcr; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013163:Splenomegaly / Q000209:etiology; D013921:Thrombocytopenia / Q000209:etiology; D013922:Thrombocytosis / Q000209:etiology
D000970:Antineoplastic Agents; D016898:Interferon-alpha; D015513:Oncogene Proteins; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C496613:BCR protein, human; D051562:Proto-Oncogene Proteins c-bcr