Analysis of a variant translocation t(11;17) in a case of acute promyelocytic leukemia (APL) led to discovery of a novel zinc finger gene, PLZF, fused to the retinoic acid receptor-alpha (RAR alpha) gene. We reviewed the clinical and molecular features of five additional patients with t(11;17)-associated APL. The clinical course of three patients was characterized by early death and three experienced disseminated intravascular coagulation. Morphologically all of the patients fell in a unusual morphologic spectrum of APL, with features intermediate between M2 and M3 AML. All six patients had PLZF-RAR alpha gene fusion as detected by reverse transcription/polymerase chain reaction assay, Southern blotting, or pulsed-field gel electrophoresis. Five of the six patients failed to achieve complete remission after initial chemotherapy or differentiation therapy with all-trans retinoic acid (ATRA). A sixth patient responded to initial chemotherapy, but on relapse failed to respond to ATRA. When tested in vitro, cultured cells from three of the patients failed to differentiate in response to ATRA. APL associated with t(11;17) and fusion of the PLZF and RAR alpha genes is a discrete clinico-pathologic syndrome with a distinctly worse prognosis than t(15;17) APL.

Between January 1985 and July 1989 we diagnosed asymptomatic stage I multiple myeloma according to Durie and Salmon [Durie and Salmon: Cancer 36:842, 1975] in 91 patients. All patients were followed without chemotherapy. Disease progression occurred in 41 patients and the median time to progression for all patients was 48 months. In the Cox multivariate regression analysis, hemoglobin levels < 12 g/dl (P < .01), bone marrow plasmacytosis > 25% (P < .01), and M-component size > or = 30 g/l for Ig G or > or = 25 g/l for Ig A (P < .01) were the only significant prognostic factors for progression. The 38 patients without any harmful factor remained free of progression for a median of more than 50 months. The 18 patients with two or three of these characteristics (high-risk group) had the shortest median time to progression of 6 months. Despite different times to progression, the response rate and survival after chemotherapy were similar for all groups of patients. Patients in the high-risk group for progression have to be frequently monitored for disease progression and might benefit from early treatment.

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To better understand the Philadelphia-negative (Ph-) chronic myeloid leukemia (CML) and its relationships with Philadelphia-positive (Ph+) CML and chronic myelomonocytic leukemia (CMML), a study was undertaken by the Groupe Francais de Cytogenetique Hematologique. Thirty-five Ph- CML patients were investigated and compared with 55 chronic phase Ph+ CML and 100 CMML patients. There were 12 M-BCR positive (M-BCR+) and 23 M-BCR negative (MBCR+) patients. No clinical or biologic differences were found between Ph+ and Ph-, M-BCR+ patients. In the Ph- group, M- BCR+ and M-BCR- patients differed significantly in age (47.7 +/- 6.6 v 67.0 +/- 6.1 years, respectively; P = .001), leukocytosis (153.4 +/- 135.1 v 58.5 +/- 37.7 10(9)/L, P = .002), relative monocytosis (1.8% +/- 1.2% v 5.6% +/- 1.4%, P = .048), absolute basophilia (8.5 +/- 9.7 v 0.9 +/- 1.5 10(9)/L, P = .001), percentage of immature myeloid precursors (IMP) in peripheral blood (29.0% +/- 9.5% v 15.3% +/- 8.1%, P = .001), and percentage of erythroblasts in bone marrow (BM) (6.5% +/- 3.5% v 14.6% +/- 3.6%, P = .001). Karyotypic abnormalities other than the Ph chromosome occurred in 0 of 12 M-BCR- at diagnosis and 7 of 23 M-BCR- Ph- CML (P = .033). None of the 13 investigated BCR- patients had detectable BCR/ABL transcripts using polymerase chain reaction (PCR) and none had an N-RAS mutation. Cytologic findings showed a marked morphologic difference between M-BCR+ and M-BCR- patients, especially in the monocytic lineage. Dysmyelopoietic features in CMML and M-BCR- patients were very similar, and the differences were of quantitative order only. Using four criteria (monocytosis, percentage of IMP, basophilia, and percentage of erythroblasts in BM), patients could be divided into typical and atypical CML and this classification correlated well with molecular findings. We conclude that, while Ph-, M- BCR+, and Ph+ CML are identical diseases, Ph-, M-BCR- CML, and CMML have many similarities and might be only different aspects of a same entity.

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