Acute basophilic leukemia

t(X;6)(p11;q23)

Disease	Rare type of acute myeloid leukemia (AML)
Phenotype / cell stem origin	Basophilic precursor.
Epidemiology	Very rare but might be prominent in infants. Four cases of acute basophilic leukemia with t(X;6)(p11;q23) translocation occurring in male infants (< 1 year) have been described.
Clinics	Hyperhistaminemia syndrome has been reported in some of the cases.
Cytology	Major component of undifferentiated blasts and minor component of basophilic blasts containing large granules reacting positively to toluidine blue staining.
	Cytology of blast cells. A: Presence of basophilic granules in the cytoplasm of leukemic cells after May Grünwald Giemsa staining. B: Positive reaction for toluidine blue cytochemistry.
Treatment	AML protocols. All patients received standard therapy for childhood AML; Two out of 4 cases reported underwent intrafamilial hematopoietic stem cell transplantation.
Evolution	The 4 patients are still in complete remission, with the following follow-ups: 24 years (P1), 18 years (P2 allografted), 4 years (P3) and 14 years (P4 allografted).
Prognosis	Good response to standard therapy for childhood AML.

Cytogenetics Morphological	t(X;6)(p11;q23)
	Karyotype of patients at the diagnosis (Patient 1: G-banding; Patient 2 and 3: R-banding). For Patient 3, the chromosome 12 is involved in the rearrangement.
Cytogenetics Molecular	Molecular cytogenetics (FISH) revealed unbalanced and more complex rearrangements than those observed on karyotype: Patient Karyotype at diagnosis / Karyotype revised after FISH analysis (BACs, Fosmids and mBAND) P1 46,Y,t(X;6)(p11;q23)[40]/46,XY[1] der(X)(6qter→6q24::6q23::Xp11→Xq13::6q22q23::Xp11→Xp22::Xq24::Xp22→Xpter), der(6)(6pter→6q22::Xq28→ Xq25::Xq23→ Xq13::Xqter) P2 46,Y,t(X;6)(p11;q23)[29]/46,XY[1] no material available P3 46,Y,der(X)t(X;12)(p21;q23)t(X;6)(q28;q23), der(6)t(X;6)(q28;q23), del(12)(q23)[18]/46,XY[6] der(X)(12qter→12q23::6q22→6q23::Xp11→Xq28::Xp11→Xpter), del(6)(q21q23),del(12)(q23) P4 46,Y,t(X;6)(p11;q23)[16]/46,XY[13] der(X)(6qter→6q24::6q23::Xp11→Xq23::Xq25→Xqter), der(6)(6pter→6q23::Xp11→Xp21::Xq24::Xp21→Xpter)
	RP11-104D9 (Red) and RP11-905P20 (Green) span the 5' part of MYB and the 3' part of MYB respectively. RP11-104D9 is delocalized onto der(X).

	Schematic representation of MYB, GATA1 and MYB-GATA1 proteins. MYB is composed of R1, R2 and R3 which are three imperfect repeats that encompass the DNA-binding domain (DBD) of MYB. TAD is the transactivation domain of MYB and NRD is the negative regulatory domain. GATA1 is composed of an activation domain (AD) and two zinc finger domains. MYB-GATA1 keeps both the DBD and the minimal TAD of MYB and the c-terminal zinc finger domain of GATA1. The breakpoint at the amino acid level is indicated by the blue arrow.
Description	The predicted fusion protein comprises the DNA binding domain and the minimal transactivation domain of MYB fused to the DNA binding domain of GATA1.
Expression Localisation	MYB-GATA1 is expressed in the nucleus.
Oncogenesis	Expression of MYB-GATA1 in mouse hematopoietic progenitors committed them to the granulocyte lineage, blocked them at an early stage of differentiation and transformed these cells.

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